Lewin Benjamin (ed.) Genes IX

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acrivation of transcription, l2l

binding site locations, )22-323, )2)f

consensus sequence,

)22, )22f

cyclic

AMP and, )21, )2If

dimer, 12l

DNA

bending

and, )22, )22f

glucose

and, J2I, 322f

monomer. 12l

mutations, 122

Cryptic satellite

anthropod,

l19, ll9f

definition

of, I I8

CTD see Carboxy-terminal

domain

CIDNA, 69

C-terminal

domains

DNA, 654

of homeodomain, 659

ofrepressor, ll0l llI

of RNA

polymerase.

648

C-value, 60-61,

60, 6ll

C-value

paradox,

Cyclic

AMP

adenylate cyclase synthesis.

121

CRP activator

and, )21, )2\f

glucose

levels and, 12 I

structure,

)21, )2lf

Cyclic

AMP receptor

protein (CRP),

361

ryI

mutations, 168

ryR

mutations,

168

Cytidine deaminase,

induction, of somatic mutations,

591-593,592f

Cytomegalovirus

(CMV

2)5

Cytoplasmic domain, 601

Cytoplasmic

inheritance, 68

cytosine

deamination,

).5, l5f, 18, l8f,502, 502f

flipping,

by methylase, 506, 506/

Cytosol.

protein

synthesis,

22O, 220f

cytotoxic

cells

(killer

T cells). 573

Cytotype,

546

Dam

methylase. DNA methylation and, 380-181,

380f,5)8

dam system,

518

Daughter

nucleoids, recondensation,

MukB and,

4r8,418f

Daughter strands.

in DNA replication, 8-9,

Deamination

of cytosine,

15, l5f, 18, l8f

of 5-methylcytosine,

l8-19, l8/

in RNA editing,

72r, 72lf

Decaping,

mRNA degradation and,

143, 143/

Degradation

bacteria

mRNA, enzymes

in, 140-I41, ).4\f

mRNA, 141-144,

l4)f, I44f

Degradosome.

in bacterial

mRNA degradation.

r41, r4tf

Delayed early

genes,

292

Deletions

definition of,

in DNA sequences,

529

frameshift mutations

and. 11, I I/

generation of replication-defective viruses,

558,558f

identifying

genes,

6),

6)f

from

immune recombination,

582, 582f

in thalassemias,

I l0-l11, I l1/

de lta elements, 5

59-5 60

Demethylases.

8ll, 8lU

Demethylation,

gene

expression atd,

6)2-6J),

6)2f,6))f

Denaturation, ofDNA,

13, 13/

De novo merhylase, 81 l, 8)

Density

gradient,

1 I 8,

1 t

Deoxyribonucleases Ses

DNAases

Deoxyribonucleic

acid Ses DNA

DHFR

(dihydrofolate

reductase),

240

DHFR

genes (dihydrofolate reductase

genel,

42,

42f

Dicentric chromosome, 539

-5

40, 5

40f

Differentially methylated

domains

(DMDs;

imprinting

control

regions; IcRs), 834,

814/

Dihydrofolate

reductase

gene (DHFR

genes), a2,42f

Dihydrouridine, 195, 195f

Dimer formation, by helix-loop-helix

proteins,

660-661,

662f

Diphtheria toxin, ADP-ribosylation

and, 172

Diploid organisms,

Dipoid

phenotypes, 49 1492

Direct repair systems,

500-501.

500, 508

Direct repeats

definition of, 524

generated

insertion, 527.527{

reciprocal

recombination between

529,

529f

in retroviral RNA, 554, 554f

Disease

genes,

RFLPs

associated

with, 58-59,

59f

Dislocalion See

Reverse lran:location

Displacement

loops See D

loops

Distances,

gerelic,3840,

)9f,

40f

Divergence

definition of, 104

of DNA sequences,

105

globin

gene,

105-106. 105f,

l06f

globin genes,

I03, 103/

rate

of,

105-106, 105f,

I06f

of repeated sequences.

rate of

neutral substitution

and, 107,

l07f

of replacement

sites, 105-106,

105f,

l06f

oI silent sites,

105-106,

105/

loops

(displacement loops)

mitochondrial origin

maintenance

388-)89,

)89f

single-stranded,

464

DMDs

(differentially methylated

domains;

imprinting

control regions;

ICRs), 834,

834/

DNA

amount,

genome

See C-value

attachment,

to interphase

malrix,

7)7-7i8,

738f

Daseparrs.

/-6, /J.6J

duplex

formation

and', l2-l3,

llf

point

mutations

of, 15

speci{icity

of replication

and

8-9,

bases,

modified,

18-19, l8f,

l9f

B-form, 8

binding

contacr

points.

27 5-277

27 5f,

27 6f

leucine

zippers and, 662-663

in minor

groove

TBP, 620-621,

620f, 62lf

to RNA

polymerase,

l-27 2,

27 2f, 27

5-27

275f, 27 6f

sigma

la(tor control

ol.

271-272,272J

centromeric,

T46

in chromosome.

24,

24l

circular

bacterial

genome,

7 )5-7

)6, 7 )5f,

7 )6f

catenation,480

minus strand,

197

plus

strand, 197

reciprocal

recombination

between

direct

repeats,

529,529f

recombination

with

linear

DNA,

460, 460f

supercoiling

of,

47 6477

47 6f

ft-acting sires,

35-)6, )rf

cls cleavage,

485-486

cleavage,

by restriction

endonuclease,

)9-4O'

40f

closed

molecule,

linking

number, 477, 478

coding

strand

sequence,

190

complementarity,

recombination

process

and,

29,2ef

conformation,

bending

cRP activator

and,

)22,

)22f

contact

with sigma

factors,

280-282,

281f, 282f

damage

methylation,

5O3,503f

RecA

protein activation,

5l l-514

repair systems.

502-50),

502f,

50)f

replication

errors,

5o2, 502f

replication

stoppage,

l-452, 452f

single-base

changes,

502,

5O2f

structural

distortior]Ls,

502-501,

502f

demethylated

regions, 832,

8)2f

denaturation,

ll, 1T

density,730-731

double-helix

mod'el,

6-8,

base

flipping,

506, 5O6f

B-ring relationship

in, 440-44I,

440f

major

groove

in,

7-8, 8/

minor

groove in,7-8, 8f

overwound,

right-handed,

twisting

number,

-47

underwound,

double-strand

breakage

by type

II topoisomerases,

479

cleavage

complex.

481,

48lf

conversion

single-strand,

4354)7, 436f

type

II topoisomerases

and,

479,481,

48lf

end, initiation

transfet

400, 400f

eukaryotic,

I l8

gene,

2-l

genetic

information

in. 5l

genetic material

in animal

cells,

iabacleia,

14,4f

in viruses,

,l-5,

genomes, 1l

hemimethylated,

)80-382,

)9of-)82f

highlyrepetitive,

I17

hybrid or

heteroduplex,

475

in breakage

and

reunion,

462464,

46)f, 464f

definition

of,

462-463

Iormation,

29-30,29f

formation

ot, 29-30,

29f

recombinants

with,

99, l00f

insertion

into

phage head, 732,

7)2f

knors, 480,481

lagging strand,

semi-discontinuous

replication,

415,

4)5f

leading

strand,

continuous

replication,

435, 4)5f

length

vints, 7)0f,

7)I

compartment

size,

7 )0,

7 3Of

linear

integration

of,

557, 557f

recombination

with

circular

DNA,

460' 460f

mainband,

ll8, l18/

methylation,

)45,

538, 632

Dam

methylase

and, 380-18i,

380f,5)8

Drosophila

melanogaster,

6)5

epigenetic

ef{ects,

819-820,

8l9f

germ

cells,

8)2-83j

histone

methylation

and, 808-809

imprinting

and,

8)2-8)4,

8))f

maintenance

of, 8)0-8)2,

81lf

targeting

for

repair

of mismatch

error

and,

508-509,

5O9f

targets, 812

Index

877

minus strand,

554-55

5, 55

5f, 7 19

modification,

promoter,

810

nonrepetitive,

I l6

nucleosomal,

7 58, 7

60, 7 6Of

cleava ge

sites, 7

64-7

65, 7 65f

corc,762-76j

ladder

organizari

7 6l-7

62, 7

6 |

length

of, 7

6l-7 62, 7

6tf, 7

length

reductions,

62, 7 62f

linker,762,763

pcriodiciry.

7 66-7

67. 7 661

rotational posirioning,

777,

777f

surface

variatiun

s, 7

6)-7 66, 7

64f, 7

6jf

translational posirioning,

77 6-777

777f

pacKlng

rau0, /)6

plus

strand,

554 555,555f

polynucleotide

chains,

6. 7, 7f

antiparallel

orientation

of,

daughter

strands,

8-9, 9f

parental

strands,

8-9, 9/

template

strands, 8-9,

protein

coding,

rearrangements,

522, 522f

transposons

aru),

528-5)0,

529f

recombination.

class switching

from.

587-589,

5gg/

renaturation,

ll, 1y

repair

systems

See Repair

systems

repetitive,117,746

replication,

429454

central

dogma

and, l0-l

l, I

DNA

polymcrases

in, 10,

4t0-41I

430f,

Btf

repression

silencers

and, 49249j

semlconservative

8-9, 9f

successive

activiLies,

448

replication

fork, 9-10,

l0/

retroviral,

554,554f

satellite

or simple

sequence,

100.

I 17,

I I8, I l8l

selfish,52l

sequences

changes,

mutations

and, l4

genome

mapping,

nonrepetitive,

6l-6),

62f

repetttlve,

6 l-61

single-strand

assembly

site or

paJ,

45 I

breakage

by type I

topoisomerases,

479

conjuga

tional

transfer

400--40

l, 4OOf,

replication,

4)54)7,

436f

strand

separation

448449,

445f,

477, 477f

structure,

)0, 47 647

8, 47

6f, 477

sugar rn,

supercoiling

See Supercoiling,

DNA

symmetry,

ll4

synthests

error-prone,507

repair,4)O,430f

replication

Sse DNA

replication

semidiscontinuous,

4)441j,

435f

telomeric, 7

49-7 50,

7 5Of

topology

manipularion

ol.

477.

477

topoisomerases

and,

847 9, 47

trans

acting

siles, ) 5-3

trans cleavage,

486

transcription,

central

dogma

and.

l0-l

l, I l/

transfer,

between

organelle

and nucleus,

72-7f

unwinding, gyrase

and,

449

writhing

number

lW).

478

dnaA gene,

)81

dnaA gene

mutations,

449

DnaA

protein

availability,

control

of, 182

binding,

to oriC, 448449,448f

replication

at origin and,

382

DNA-arrest

mutants,

447

DNAases

(deoxyribonucleases)

definition of, l0

chromatin

digestion,

7 88-7 89, 7

DNA

cleavage sites, 7

65, 7 65f

hypersensitive

site

creation, 786-788,

787f

single-strand

nicks in

DNA, 7$-764,764f

II,

single-strand

nicks in DNA,

76)-764

DNA-binding

domains

function,645

homeodomain,

65 8-660,

659

66Of

independence

from

transcription

activation,

64)-645,

644f

localization,

of transcription-activating

domain,

647,

647f

specificity,

for target promoter

or enhancer,

646-647

steroid receptors,

654

tethering

function,

645

transcription

activation

specificity and,

644-645,644f

types,

65I-652,

652f

zinc finger

moiif,

651, 652-653,65)f

DNA-binding

proleins,

449

DNA-binding

sire,

109

DnaB

protein

oric replicon,

419

prepriming,

448,

448f, 449

replication

fork

and,44l, a42f

DnaC

protein,

prepriming,

448,

448f,449

DNA-delay

mutanrs,

447

DNA-dependent

prorein

kinase

(DNA-PKcs),

516-517,

5t7f

DNA

lingerprinting,

I l8

DnaJ

protein,

DnaK

protein,

45 I

DNA ligase

AMP inrermediare,

444,

446f

Okazaki fragments

linking

and, 443'444,446f

DNA mapping

techniques,

restriction

endonucleases

and, 1940,4Of

DNA methylases,

8)I, 83lf

dna mutants,

4294)0

DNA-PKcs

(DNA-dependenr

prorein

kinase),

516-517,

5t7f

DNA

polymerase

a,444

44044r,

44of,

44rf, 444

catalytic

activity, 434

catalytic

core,

44I, 441f,442f

clamp loader,

4)9,

Bgf

6, function

of, 444445

in DNA replication,

43O4)t,

4)0f.43tf

e, function

of, 444

enzyme

units

lagging

strand

synthesis

and, 442,

4Bf

leading

strand synthesis

and.

442,443f

error-prone,592

errors during

replication

frameshifts,

412

substitutions.

432

eukaryoric,

4jo4)1,

4jtf

elongation,

444445

initiation,

444445

exonucleolytic

activily,

4)24)4,

4)3f

fidelity

of replication

and,

4J24r,

4iJf

function

of, I

r,4)t-4j2,4)2f

III

holoenzyme

subcomplexes,

$9440, 4j9f

replicase

activity of, 431

replication stall,

DNA damage

and, 507

IV, complement

synthesis

to damaged

strand, 507

nuclease activities,

4)1432,

$2f

l'-OH end or

primer,

4)74J8, 4)7f

priming

requirement,

188

prokaryote,

4)0,4)lf

pyrimidine

dimer and,

510

replication

at 5' end and,

394, )94f

sliding

clamp. 440441, 440f,

441f

structure, commonality

of, 43)4)4,

433f,4j4f

subcomplexes, 4J9440,

89f

V, complement

synthesis

to damaged

strand,

i07

DNA repair

deficiency diseases,

5 l7-5 l8

DNA repair

synthesis, 4)O,4)0f

DNA

replicases

definition

of, 430

functions,

441, 441f, 444445

DNA

replication

initiation, priming

for,

4)7 4j9,

4)7

438f

semi-conservative,

430,

4301

DNA restriction

analysis.

Sae DNA fingerprinting

DNA sequences, protein

coding, for

more than

one

votein,

4547, 46f, 47f

Domains

chromosomal

active

genes

and, 7

88-789,789f

definition

of, 790

DNA supercoiling

in, 7]5, 7)5f

eukaryotes, 736-7)7,

7)7

insulator

sites, 7 90-7

9\, 7 91f

LCR

control of, 789-790,790f

locus

control region, 790-791,

79lf

matrix attachment

sites, 790-791,

79lf

regulatory,

7 9O-7 9

I, 7 9 lf

DNA-binding.

See DNA-binding

domains

Dominant

negative,

I l0

Dosage

compens ation,

826, 826f

doublesex

(dsx) gene,

686-687

Double-strand

breaks

(DSBs)

generation,

critical

points,

589

in immune

recombination,

582,582f

initiation

of homologous

recombination,

464465,

465f

of mating type

switching,

491494,494f

repair

systems,

r00f, 501,

516-518,

517f

synaptonemal

complex formation

and,

467469,468f

target,

gene

as, 7 I 5-7

| 6, 7 I 5f

Double-stranded

RNA

(dsRNA),

degradation

mRNA,

343-145, )44f,

)45f

Doubling

time, 410

Down mutations,

274

Downstream,

258

DP thymocytes,

598

Drosophila

melanogaster

bithoru locus,

7 85,

825

chromosome

banding

pattern,

7 42-7

$, 7 43f

centromeres,

742-743

DNA, centromeric,

746

DNA

methylation,

635

embryonic

development,

65 l

eye color,

position

effect

variegation,

B2O-821,

82lf

Fab

7 region,

7 85-7

86, 7 85f

gene

expression

map, 94

genes

Antp,824

brahma,824

emc,66I-662

essential,

number

of, 90-91

Eu(var),81I

872

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447

Gene duplication See

Duplication

Gene expression

activation,

histone acetylation

and, 805-806, 805/

alternative,

46, 46f

in bacteria. ll

control, 102 Sde a/s, Ttanscription; Translation

in bacteria, 302

chromatin structure and,

7 97

in eukaryotic cells, 302

demethylation and, 632-637, 632f, 6)3f

in embryonic development, 53

En element and,

542-544,543f

eukaryotic,

control by of initiation of transcription,

64t-642,642f

inactivation, by antisense RNA, 338-339,

339l

levels of, 92-9),92f

number, 9l

preferential

digestion and, 7 88-7 89, 7 89f

processes

i^, ))-j5, 34f

silent mutations

and, 105

Spm

element and, 542-544, 54)f

stages, transcription See Transcription

systematic analysis, by

RNAi,

344

two-stage

proces

129, 129f.

See 4lJo

Transcription;

Translation

visualization,

direct,

741

Gene families

definition

of, 5I, 99

divergence of repeated sequences, rate of neutral

\ubstilution and, 107, l07f

in human

genome,84-85

members, 99

number of,

genome

size and, 81, 81/

pseudogenes

in, 108-I09

relatedness of members, 99

superfamilies, 5l

Gene 44

prcdnct'

447

Gene 62

products.

447

Gene 12

protein,

326-327, 326f, 327f,

446

Gene 6l

protein,

446447

Gene

protein product,

General factors

(basal

factors), 6 I I

Genes

activation,

undermethylation and, 6ll

active

chromosomal domains

and, 7 88-7 89, 7 89f

derermination

of, 65-66

inactive

versions of See Pseudogenes

organizational

patterns

in, 581

Y chromosome, 86-87,87f

alternative or overlapping, 53 See

also Alleles

codirrg,23-36

fnrnrntein )L-')\ )af

for

proteins

with

alternative slafts, 4546,46f

for

RNA, 25, 25l

for RNA, identification oI, 67

as coding

unit, 2,

colinearity

with

prcre\n,

32-)), 33f

complement, 26

converslon

genetic

recombination and, I I6

interallelic recombination and,

547 6,

47 5f

definition of,

2-3

distances

in, )8-)9, 39f

distribution,

genome,

85-86, 85f

duplicated

differences

in, 100-l0I

retention of function,

I 15

essential, number of, 89-92,

90f, 9lf

expressed number,

in eukaryotes, 80

measurement of

9)-94,

94f

extranuclear,68

Iunctional vJ nonfunctional,

102

functions, redundancy

of, 9l

identification

by conservation of exons, 6J-64,

63f-65f

by conservation of

genome

organizaliol].,

65-67,

66f,67f

homology with other species,

78-79

imprinted, control of, 834, 834f

inactivation, heterochromatin

extension

and, 82

82rf

interrupted See Interrupted

genes

length of,

j3-74,34f

mispairing,

I l6

nonallelic, exons in, I

nontranscrjbed,

7 7 7

-7

7 8. 7 7 8[

number of

in bacteria,

77-79,78f

different

organisms.

77f

in different species,

7 8f

in eukaryotes,

79-8o,79f, 80f

genome

size and,78,

78f

in human

genome,

83-85,

84f

in mouse

genome,

81,

overlapping, 4547,

46f,47f, 5)

protein-coding,

70-7

1, 7Of, 82

related, development by

duplication,

<imnlcc Inrm ?R

sizes, differences irr, 4)45,

44f,4rf

structural,

j02.

See also

lac

genes

transcribed,

777

-77

8, 77 8f

types,

number of

8I-83, llf,

82f

Genetic

code, f89-2 I 5

anticodons

See Anticodons

breaking,

190

codons. See Codons

definition of,

evolution, I92

fixed starting

point

for, l0

reading

frames, l1-12

sporadic alterations,

197-199,

197f,

l98f

universality,

19l-192

Genetic

information

central dogma,

10-1 I, f l/

DNA base sequences

and, 6

expression,

as unidirectional,

I I

positional,53

Genetic

linkage, 24

Genetic linkage maps, 56

Genetic locus, 24

Genetic mapping

minisatellites for, 123-125,

124f,

l25f

RFLPS

for, 58-60, 59f

Genetic

recombination,

gene

conversion

and,

I l6

cenetics, history of, 3l

Genome

bacterial, nucleoid,

7 ) 4-7 ) 5,

7 ) 4f

contents ot,

2, 55, 57-58, 58J

definition of,

DNA in, I I

extrachromosomal

bacteriophages

See

Phages

plasmids

Sea

Plasmids

gene

distribution

85-86.

85J

genes

in,

human, number oI

genes

in, 83-86,84f

individual

variation in. 57-58,

58[

mapprng

by linkage,

restriction cleav

age, 56-57

by sequence,

minisatellite

vari abllity,

124, l24f

number

genes

in, 56

organelle

Sae a/so

Mitochondria,

genomes

DNAir', 67-69,

68f, 69f

potential

of,

sequences,

number

genes

and,

77, 77f

size,12,

l2f

in different

phylum,

60-61,

60f, 6If

in different

species,

7 8, 7 8f

gene

number

and,

78, 78f

genetic

complexity

and, 6l

length

of nonrepetive

DNA and,

number

gene

families

and, 81, 8l/

proportion

unique

genes

and, 81,

8l/

protein

binding and,

3 17

qpes,12,

I2f

viroid,

I9-20,20/

virual,

Germ

cells,

methylation,

8j2-871,

81)f

Germline

pattern,

577

Gerstmann-

Straussler

syndrome,

839

y-globulin gene,

633

GGQ

motii, 174

GlcN6P

activation

ribozyme

that cleaves

mRNA,

)40,34rf

regulation,

7 l4-7

15, 7 l4f

Gln/Asn

protein,

prion

formation

and, 838

Globin

gene

deletions

in thalassemias,

I I0-l I I,

I I I/

during

development,

I0l-102,

102,f

exons,5l,5l/

intron

length, 4l

cluster

formation,

102-107,

103,

deletions

in thalassemias,

I I0-l

I I, I I l/

during development,

l0l-102,

102/

exons,

)I, )rJ

goat,

I09

intron

length, 4l--42

pseudogenes,

I09

restriction

map,

40, 4ll

species

diflerences,

43,

4jf

clusters

evolution

of, I

I t-I l2

formation

by duplication,

l0l-104,

lo2f, l0)f

divergence,

105-106,

lo5f, l06f

evolution,

103-104,

LO)f, 106,

l06f

organization,

structural,

41,42f,

l0l, l02f

pseudogene, I08, I08/

superfamily,

51, 5ll

Globin

protein,

synthesis,

l)3-134,

lj4f

B-Globulin

gene

DNAase

I digestion,

88-7

89,

89f

LCR,789-790,

790f

p-Globulin

promoter, hlryersensitive

sites,

787

Glucocorticoid

receptors

activation,

ligand binding,

656,

656f

zinc

fingers, 615-656,

656f

Glucose,

CRP

activator

and',721,

j22f

Glutamate

receptors,

mRNA

editing,

721,

72lf

Glycolases,

base

flipping,

506,

5o6f

Glycosylases,

excision

repair

in mammalian

cells and,

504-50r,505f

GMP-PCP,

I68

phase,387,787f

Gratuitous

inducers,

307

GRE

(glucocorticoid

response

element),

649

Index

875

GT-AG rule,

671

GTPase center,

179

cTP-binding proteins,

protein

synthesis.

t79

GTP hydrolysis

activation,

of ribosomal

translocation,

I72

aminoacyl-IRNA

entry into

A site

and,

r67-168,

t67f

initiation factors

and,

165-166,

t65t', t66f

mismatched

aminoacyl-IRNA

and, 2l I

in SRP-receptor

inreractin.

2]1,

8lf

Guanine,

Guanine nucleotide,

self-splicing

reaction,

7Og,7OSf

GUG codon, in

protein

synrhesis,

58-160,

160/

Guide RNA, 7

22-7 24, 7

23f, 7 24f

Gyrase

DNA unwinding

and,,449

enzyme turnover,

482

signal

inversion

model, 481482,

482f

structure, 48

H/ACA

snoRNAs

699-7OO,700f

Haclp transcription

factor.

693,

69}f

H a e n o

h i I i u

u e n

nomt

gene

number

in. 78

size, family

size and, 8 I,

8l/

Hairpins

at coding

end, in immune

recombination,

jB4-jBj,

585f

formalion,

59O,590f

Hammerhead

ribozyme

Mg2+ initiation

catalysis,

7 t9-720,

72Of

self-clevage,

7 19, 7 19f

H antigen

antigen).

Haploid

phenotypes,

49 t492

Haploid-specific

f unctions,

49O, 49Of

Haplotype,

59-60

Haptens,

575,591

HATS

See Histone

acetyltranslerases

Hbanti-Lepore,

lll

HbH

(hemoglobin

H),

1l I

HbKenya, I11-112

HbLepore,

lll

HDA

(high-density

oligonucleotide

arrays),

measurement

of mRNAs,

94,

94l

HDACs

See Histone

deacetylases

Headshell,

DNA

Iength

in virus

and. 7)I-7l2,7)2f

Heat-related gen

es, 27

8-27 9

Heat

shock

genes,

649-650

Heat

shock

proteins

hsp70

genes,

scs

and scs'

elements,

78J-784,

7S3f

Hsp70

system,

225-226,

225

226f

Hsp90

system. 225-226,

226f

Heat shock

transcription

factor

(HSTF),

650

Heavy

chains,

in antibody

tetraner,

575-576,

j76f

Heavy strand,

120

HeLa/SV40

cells,

replication

appar

atus,

447

Helicase-primase

complex,

Helicases

DNA unwinding.

4)5-4)6.

4)6f

hexameric,

4J6,4)6f

priming

requirement,

418, 418/

stbrnir,

625-626,

627

Helix-loop-helix

motif

(HLH).

651

Helix-loop-helix

proteins (HLH

proteins)

basic

or bHLH

proteins,66l-662,

662f

dime r formation,

660-66t,

662f

interaction,

by combinatorial

association,

660-662,

661f,662f

nonbasic,

661-662,

662f

sequence

motif,

660-661,

66U

Helix-rurn-helix

model,

of repressor DNA-binding,

)62,362f

Helix-turn-helix

motifs

definition

of, 651

f unctions/roles

) 62,

3 62f

lambda repressor,

362,

j62f

Helix-turn-helix

region,

Cro and repressor

in, 37 I

Helper

T cells, 572

Helper

virus, 558

Hemimethylated

sires,

83 l, 83 l/

Hemoglobin

adult vs embryonic,

l0I-i02, 102/

synthesis,

\)3-134, l)4f

Hemoglobin anti-Lepore,

I I 1

HemoglobinH(HbH),

lll

Hemoglobin

Kenya,

I I l-l 12

Hemoglobin

Lepore,

1l I

Heterochromatin

absence

histone

acetylation,

808

constitutive, 7 40,

826-827

definition

of, l19, 739,7)9f

epigeneric inheritance,

820, 820f,821,

821f,

8)5-8)6,836f

extension.

gene

inactivation

and,, 821, 82lf

facultative,

827

f ormation,

e a{, 82)-824,

823f

insulators

and, 782

interacrions,

with histone,

822-824, 822f,

82)f

propagation,

820-821,

82lf

satellire

DNA and, I t7-l

19, tt8f,1t9f

self

-assembly.

835-8)6.

8t6f

self-assemblying

complexes,

820, 820f

Heterogenous

nuclear

RNA

(hnRNA),

669,669f

Heterogenous

ribonucleoprorein particle

(hnRNP),

669,669f

hflA

gene

murations,

174

HflA host

protein,

368

hfl

gene

mutations,

f 74

Hfq

prorein,

142

Hfr

(high

frequency

recombinarion),

401

H)/H4,82)

High-density

oligonucleotide

arrays

(HDA),

measurement

of mRNAs,

94, 94l

Highly repetitive

DNA,

t 17, I l8

him

genes,486

Hinge

region,

of repressor,

I I 0, I I I

HIRA,774

Histone

acetylation,

801-804,

80)f, 8O4f

activation of

gene

expression

and,

805-806,805/

epigenetic

inheritance,

8j6,

8)6f

HATs and,

806-807,

806f,8O7f

HDACs

and.

806-807,

807f

replication

and,

807

reversibiliry,

806

transient

at replication,

805, 805/

cote. 7 59-7

60, 760f,7

67-7 69, 7

67f-769f

oellnrnon

ot, /)6

Hl, 760,763,

770

Hj,760,767

H4,760,767

H2 A-H28,

disassembly,

7 81, 7

82f

H2A-H2B

dimer, 7

67, 7 67

77 2, 77

)

H32-H42

tetramer,

67-7 68, 7 67f, 7

68f,772, 77

H) J varrant,774

interactions,

with heterochromalin,

822-824,

822f,82)f

methylation

DNA merhylation

and, 808-809

HPI

binding

and. 822,822[

modifications,

802-804,

80l, 80jf,

804, 804f

tail, 812, 8l2f

by methylation,

80), 803f,8O4,

804f

phosphorylation,

803, 801, 804,804f

sites, 803, 803/

nRNA,,

697, 697f

octamers

in chromatin

remodeling, 799,799f

conserveo, / /2.

/ lzJ

disassembly

of,

77),

77)f

displacement by transcription,

779-7

81,,

779f,780f

Iormation of

-7

69, 7 67

f-7

placement

of, 776

reassembly

oI, 77 2-77 ), 77

phosphorylation,

chromatin

structure and,

8 I0-8 I I

8r 1f

preformed,

770,77Lf

Histone

acetyltransferases

(HATs)

activators

and, 806-807,

806f, 807f

active

inactive

chromatin

and, 809,809f

Histone

deacetylases

(HDACs)

activators

and, 806-807,

807f

active

inactive chromatin

and,

809,809f

repressors

and, 808, 808/

Histone fold,

768

Histone methyltransferase

SUV39Hl,

822,

822f

HLA locus,

599

HLH

(helix-loop-helix

motif),

651

HLH

proteins

See Helix-loop-helix proteins

H2 locus,

599

HMI locus

telomeric silencing,

821, 82)

unidirectional

transposition

and,

493, 494

yeast

mating

type and, 488489,489f

I1MR locus

telomeric

silencing, 82I,

823

unidirectional

transposition and,

49), 494

yeast

mating type

and, 488-489,

489f

hnRNA (heterogenous

nuclear RNA),

669,

669f

hnRNP

(heterogenous

ribonucleoprotein particle),

669,669f

HO endonuclease

cleavage oI MAT Iocus,

4%-494,

494f

production,

regulation

of, 494496,

49 5f

transcription,

49 5-49 6, 49 5f

Holliday

junctions

genelation,

by RecA,

472

resolution,

46), 464f,

468469

by Ruv

system, 472473,47)f

Holoenzyme (complete

enzyme\, 265

Homeobox-containing

genes,

658

Homeodomain

definition of, 65 I

Drosophila

melanogaster,

658-660,

659f,

660f

helical

regions,

659, 659f

Homeodomain-containing proteins,

660

Homologous

end-joining

(NHEJ).

516-518,

517

Homologous

recombination

branch migration,

46), 463f

breakage and reunion,

461, 46If,462-464,

46)f,464f

hybrid

DNA and, 461462,462f

initiation

double-strand

breaks

and, 464-465,

465f

endonuclease,

464

between

synapsed chromosomes,

460462,

46rf,462f

hop2

mutation, 469

Hotspots

definition

ol, I04,470

for

mutations,

17-I8, l8f

876

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Locus control region

(LCR),

789-790,790f,791

Long interspersed repeated segments

Sde LINES

Long

patch

pathway.

for excision repair

in mammalian

cells, 505, 505/

Long

terminal

repear rLTR),

555

Loss-of

-function

mutations, 27

LPS

(lipopolysaccharide),

602

LSDI

(lysine-specific

demethylase),

808-809

LTR

enhancer,557

region,557

LTR-containing retroposons, 563

LtR-pol-LTR, 559

LTRS, 556, 557

Luxury

genes,

Lyases. excision repair in mammalian

cells and,

504-505,505f

Lymphocytes See alsoB cells; T

cells

development, IgM synthesis and, 586-587

lmmalure,

poot

oL > /+) / ), > /+l

target cell identification, 575

Lysine-specific

demethylase

(LSD

808-809

Lysis, 150

Lysogeny

balance with lytic cycle, critical stage,

)7)-)74,37)f

control circuit, 168

definition of.,

35O, )51, )93

pathway,

)68-)70, )69f

repressor dimeric structure and. l6l

repressors and, )65-366, 165f

requirements, cII and CIII

genes,

)68,368f

Lytic

cycle,

balance with lysogeny,

critical stage,

17)-)74, )7)f

Macromolecular assembly, synthesis, autogenous

regulation oI, 327

-)28,

328f

Mad:Max heterodimer, 808

Maintenance

methylase, 83 l-832

Maize

clonal analysis, 5)8, 5)9f

transposition,

5J8-540, 5i9f,

540f

Major

groove,

of DNA double helix, 7-8, 8/

Major histocompatibility complex

(MHC)

class I antigens, 599

gene

organization

601, 60lf

structure, 601, 60U

class II antigens, 600, 60I, 60I/

coding of immune system

genes,

599-602,

600f,60rf

definition of. 571

Mammals

DHFR

genes,

42, 42l

DNA, mitochondria, 70, 70f

excision-repair

pathways,

504-505, 505f

genes,

exons,

43,44f

genomes,

ll7 See also Hnman

genome

endogenous retroviruses, 561

G-C content

in, 741,74lf

mitochondrial,

70-7I

size

of, 8l

HPt

822-82), 822f, 823f

MHC regions, 600, 600/

nontranscribed spacer length, I l4

prion

diseases, 8)9-840, 8)9f

repair systems,

5 1 5-516

replication. of mitochondrial DNA, 189. 189/

satellite DNA, hierchical

repeats,

I20-121,

r2rf-r23f

surveillance

systems,

145, 145/

X chromosome, dosage compensation,

326, 826f

MAPK

(mitogen-activated protein kinase), 604

MARS

(matdx

attachment regionsl,

7)7-7)8,

778f,79r

Maternal inheritance,

67-68,

69f

Mating type switching

by HO endonuclease expression

regulation,

494-496,495f

mother cells a.nd, 495,

495f

M,4T locus

cleavage. by HO endonuclease,493494,

494f

mate type switching, 493-94,

494f

regulator

protein

coding,

490-492,

49Of, 49),f

yeast

mating type conversion and,

488489,

489f

Matrix attachment regions

(MARS).

7)7-7)8,

7)8f,791

Maturases

aulosplicing

introns

and.

7 1 6. 7 17.

7 17f. 7 I8J

endonucleases and.

716. 7 17. 7 17

7 l8f

(megabase pairs),

MCH

protein,

T cell receptor and,

597-599,598f,599f

MCM

protein (minichromosome

maintenance

protein).

j86-)88,

)87

Mediators, 648

Megabase

pairs (Mb),

Meiosis

bivalents, 29,

29f, 461

checkpoint

system, 469

crossing-over, 29, 29l

extended,

lampbrush chromosomes

and,

741-742,742f

in harar^?!,d^ro /7q

recombination events and, 468469,

468f

srages,

homologous recombination

during,

46t,46rf

timing of events,

468, 468f

Melting. See Denaturation

Membranes,

protein

insertion

mechanism of, 2)8-240,

2]9f

posttranslational,

leader

sequences

and,

240-24r, 240f

Memory cells, 575, 594

Mendelian inheritance,

restriction sites

and, 58,

58/

Mendel's laws,

Meselson-Stahl experiment of

1958, 9,

Messenger RNA

(nRNA),

127-148

abundant, 92-93

bacterial

life cycle of., 135-l)7

1)5f, l)6f

protein

synthesis

in, l)4-1)5,

I35f

base

pairing

with

IRNA, in

protein

synthesis

initiation, l6I-162, l6lf,

I62f

binding of

p32,

)27, )27f

coding

region, I 36

decapping,

14), l4)f

degradation, I4)-145,

143f, 1.44f

destabilizing elements,

141-l

43, l42f

3' end,

generation

of, 695-697

695f,

696f

5' end,670

eukaryotic,

134,

695-696,

696f

capped

5'end, 138-l)9,

I38f

life cycle ol. l)7-l)8.

l38f

poly(A)+,

179-140,

140f

transcdpt modification,

lj7,

l37f

export, RNA splicing

and, 682-68),

682f,68)f

functions, I28,696

l|,istor'e, 697, 697f

hybridizarion with cDNA,

92-9),

92f

initiation sequence,

2l I

interactions, with rRNA,

180

localization,

1 46-1

47, I 47

measurement of,

93-94, 94f

monocistronic,

I36

nucleotide sequences

coding

region, ll, l4l

lead,er,33,74f

lrarler, )3,34f

nucleotide

triplet, 130

poly(A)+

isolation

of, 140,

l40f

removal, inhibition

of translation

and, l)9-140

poly(A)-fraction,

140

polycistronic,

intercistronic

regions

ol, l)6, l)7f

polysome

and,

l3?-1j4,

l34J

pre-nRNA

processing,

)4,

)4f

production,

RNS splicing

and, 669

purification,

cloning

approach

for, 140

retroviral,552

RNA editing,

720-721,

72Of,72rf

scarce, 93

secondary

structure changes,

332

size

of, 128f

30S subunit,

I79

stability

protein

synthesis

and, I 16

sequence

and,

I4l-147,

142f

structure and,,

1 41

-I

43, I 42f

structure

adive

cenrers,

177-178,

178f

l'terminal

stretch of

A residues or

poly(A)+,

r)9-r40, r40f

surveillance

sysrems,

I 44-l

45, l. 45f

synthesis,

73, 33f,

)8, 38f, 618

3'terminal

end,

670

transcription,

I29, I29f

in bacreria,

lj5-136,135f,

I)6f

eukaryotic

prokaryotic,

610-61

translation,

I29,

1,29f, 163

in bacteria,

I)5-I)6,

lj5f, 136f

in eukaryotic

cells,

135

protein-synthesizing system

for, 130

ribosomes,

l)2-l)),

l1)f

transporr,

145-147, l45f

5' untranslated

gion,

) 40, 341

untranslated

region or 5r

UTR, ll6

Metallothionein

gene

response elements,

650-65t,650f

Me thanococrus

annaschii,

7 I

Methionine,

protein

synthesis,

I 58-l 59,

59/

Methylases

base

flipping, 506,

506f

DNA,8]I,83I/

Methylation

capped

on 5' end

of mRNA,

l)8-Ij9,

l38f

of Cpc

islands, 615

DNA See

DNA, methylation

histone, DNA

methylation

and, 808-809

rRNA, snoRNA

base

pairs

and, 699,

699f

of transposons,

plants,

542

5-Methylcytosine,

deamination,

I8-I9,

I 8/

Methyltransferases

base

flipping, 506

DNA.8lI, 83r/

Met-rRNAi,

r 65-1 66,

1 65f, I 66f

MFD

protein,

stalled

RNA

polymerase

and,

625-626,626f

MHC

see Major

histocompatibility

complex

Mice Sea

Mouse

Michaelis-Menten

kinetics,

ribozyme

catalytic

readlons ano,

/ IJ, /

rtl

Index 879

Micrococcal nuclease

chromatin digestion.

759, 759f,

76t, 778-779

cleavage reactions,

5-77 6

reduction

oI nucleosome

monomer

length,

7 62-763, 7

62f, 76)f

transcription

and, 77 8-779

MicroRNAs,

)42-3 4),

34jf

Microsatellites

definition of, i24

replication

slippage, 124-125,

l25f

unstability

of, i24-125

Middle

genes,

282,28)

Min

CiD, 415,4l5f

Miniature

interverted-repeat

transposable

element

(MrTE).

561

Minicells, 4l

Minichromosome

maintenance protein (MCM

protein),

)86-188,

)87

Minisatellites

definition

of, 100

for

genetic

mapping,

123-t25,

t24f,

t25f

Minor

groove,

of DNA

double helix,

7-8,

Minus strand

DNA, 554-555,

555f.7t9

Minus

strong-stop DNA,

55,1-555

Mismatches

ofbasepairs, l8-19

protein

synthesis

errors, I

56, I 56/

repair

systems,

500, 501

base excision,

500, 501

directional control,

507-509,

508f,

509f

nucleotide

excision,

5001

501

Missense mutations

definition

of, 172

tRNA, 206-207

2O7f

Missense suppressors,

206-207,

207f,

2O9

MITE

(miniature

interverted-repeat

transposable

element),

561

Mitochondria

chaperone

activity,

244

daughter, 424425,424f

division, dynamin

and, 414

DNA,

68-69

circular,69

human, 70, 70/

variable organiza

tion

of,

7O-7

l, 7

0f, 7 If

evolution

by endosymbiosis,

72-7j,

7 2f

genetic

code

changes, 198,

198/

genomes,

distribution

genes

in,

69-7O,70f

stze

of., 69

somatic

variation,

67, 68f

origins, D loops

and,

388-389,

)89f

protein

leaders,

240

protein

synthesis, 240

replication,

424425,

424f

segregation,

424425,

424f

TIM

complexes,

243, 244,

244f

TOM complex,

243-244,

24)f

Mitogen-activated protein

kinase

(MApK),

604

MMTV

promoter,

802

mod(mdg4

)

gene,

7 84-7

85, 7 85

Monocistronic

mRNAs,

I l6

Monster particles,

7f 4

MotA

phage-encoded

product,

355

Mouse

aj3-globulin gene,

109

centromeres,

satellite

DNA

in, I I 9,

I l9/

DNA, ll8,

tt8/

Gapdh

gene,

genome

divergence

of repeated

sequences.

rate

o{ neutral

substiturion

from,

IO7

IOTf

880

Index

number

genes

in, 83,83f

sequences, vs

human

genome

sequences,

66-67, 67f

innate

immune response,

604

MHC regions,

600, 600/

pseudogenes,

satellire DNA

hierarchical

repeats in, 120-12),

l2lf-12)f

quarter-repeats

120-12I, l2lf

somatic mutations, immune

diversity and,

590-59r,59rf

MRE

(multiple

metal response

element). 650-651

mRNA

See Messenger RNA

MSH repair

system, 5O9, 592

Mspl cleavage,

632-6)), 6j2f,63)f

MIDNA,

MTOCs

(microtubule

organizing centers), 745

MUA

protein,

530-5)l, 53lf

MUA transposase

5)O-5)l, 53lf

MUB

protein,

531

Mud2

protein,

677

mudrA

gene,

541

mudrB gene,

541

muk

gene

mutarions, interruption

of segregation,

4t8, 418f

Multicopy

inhibition,

5)7

-5)

8, 5J7

Multimeric proteins,

109-l 10, I l0/

Multiple alleles, 27

-28,

28f

Multiple

metal response

element

(MRE),

650-651

Mutagens

acridines

SeeAcridines

induced mutations

and, 14

point

mutations

and, l6

Mutants

constitutive,

108

uninducible, 108

Mutations

advantageous,

1 04

back, I

6-17

background level,

in bacterial

division or segregation,

cell shape and

4t24r),4rJf

causing

deafects, 91, 9ll

changes,

neutral, 104

cts

acrrng,

pailitioning,

41 7

4\ 8

cls-acting sire,

108-109. 108/

in consensus

sequences, 7

l0-7 l\

control sites, .rs-acting,

15, l5l

deleterious,

104, 108, 108/

deletions, l6

in different

genes,

26, 26f

DNA

sequence

changes and, l4

effects

of, 26, 27f

evolurion and,

exon,

j9,

favorable,459

lorward,

t6-17

frameshift,

31, 31/

gain-of-function,27

hotspots, 17-t9,

t8f, t9f

induced,

insertions,

inlron,

)9,4j

leaky,26

linear

arrangement

ol, 24

loss-of-function,

nonlethal,

causing

lethality in

combination,

9r-92,9rf

nonsense

oellnllton

ot, I /z

nRNA degradation

and,

144-145

|RNA, 206-207,

206f

point,

promoter

characterization,

6l)-6]14,

614f

pseudogenes,

1 08, 1

08/

rates, reduction by repair

systems, l8-19

recessive,

gene

function and, 25,

25f

in replacement

sites, 105

in same

gene,

25-26,26f

second-site reversion of, l7

silent,27,27f

in silent sites, 105

spontaneous, 14,

567

<rrnnre<<inn n{ | 7

trans-actrLg s]te

nrrtiiinnino 417-4lR

prorein,

16, 16l

regulator

gene

identification

and, )09,3O9f

true reversion

ot,

l6-17.

l7J

unfavorable,459

Mutator

phenotype,

507

Mutator

transposon, 54I

mut

gene,

activities, 507-5O8, 508f

MUISL system, 509,509f

Mymplasma

capricolum,

genetic

code changes,

I 97

Myc

proteins,

661, 662

Myoglobin, in

globin

superfamily, 51,

NAD

(nicotinamide

adenine dinucleotide),

172

Nascent

protein

definition of, I

ribosome

and, 179

translocation

into ER, 2J2-233,

2Bf

Nascent RNA, I

Natural selection

89, 91-92,

459

Negative

complementation,

310, )IOf

Negative regulation,

/ac

gene

control

and,,305,705f

Neurospora trassa,

q,tl8

mutant, 709

Neutral sites, rate of substitution,

lO7, l07f

Neutral substitutions,

NFI binding, nucleosome

and, 8O2,802f

NF-KB

factor,

652

NF-xB-like

pathway,

601

N-formyl-merhionyl-IRNA (rRNArMet),

t58-ti9,

t59f

NHEJ

(homologous

end-joining),

516-518, 517f

NHEJ

(nonhomologous

end-joining),

586

Nicking

of DNA supercoils, 736

in immune

recombination,

584, 585f

initiation

of nonreplicative

transposition,

5)), 5)Jf,

534

of transposition,

570, 510f

nucleosomal

DNA, 763-764,

764f

with

phage

protein,

conversion

double-strand

to single-strand DNA,

4)6-4i7,

B6f

resolution

of Holliday

junction.

46), 464f

retrotransposition

oI non-lTR

elements nad,

,66,566f

in T-DNA

transfe\ 405406,405f

Nick translation, 4)2, 4)2f

Nicotinamide

adenine dinucleotide (NAD),

I72

Nijmegan

breakage syndrome,

5 17

-5

| I

Nitrogenous bases, in nucleic

acids,

Nitrogen starvation,

Escherichia coli,

279

N nucleotides,

584-585,

585f

Nonallelic

copies, t02

Nonallelic

genes,

exons in. 1 l6

Nonautonomous

controlling

elements, 540-542,

54lf

Nonhistone

proteins,

{unctions,

759

Nonhomologous

end-joining

(NHEJ),

586

Nonhomologous

recombination,

replication-def

ective

viruses

and, 558, 558f

Non-Mendalian

inheritance,

maternal,

67-68, 69f