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that it enables

RNA

polymerase

to

read

through

a terminator,

thus

extending the RNA

transcript.

In

the absence

of the antitermination protein,

RNA

polymerase

terminates at

the terminator

(top

panel).

When the antitermination protein

is

present,

it

continues

past

the terminator

(mid-

dle

panel).

The

best-characterized

example

of antiter-

mination

is

provided

by

phage

lambda,

with

which

the

phenomenon

was discovered.

It is

used

at two

stages of

phage

expression.

The

antitermination

protein

produced

at each stage

is specific

for

the

particular

transcription

units

that

are expressed

at

that stage,

as summarized

in the

bottom

panel

of Figure

ll.r2.

The

host

RNA

polymerase

initially

rran-

scribes two

genes,

which are

called the imme-

diate

early

genes.

The transition

to the next

stage

of expression

is

controlled

by

preventing

termination

at the

ends of the immediate

early

genes,

with

the result

that the

delayed

early

genes

are expressed.

(We

discuss

the overall

regulation

of lambda

development

in

Chapter 14,

Phage

Strategies.)

The regulator gene

that

controls the

switch

from

immediate

early to

delayed

early expres-

sion

is identified

by mutations

in lambda

gene

N that

can transcribe

only

the immediate

early

genes;

they

proceed

no further

into

the infec-

tive

cycle. There

are

two transcription

units of

immediate

early

genes (transcribed

from

the

promoters

P1 and

Pp). Ttanscription

by E. coli

RNA

polymerase

itself

stops

at the terminators

at

the ends

of these

transcription

units

(41

and

/p1,

respectively.)

Both terminators

depend

on

rho;

in fact,

these

were

the terminators

with

which

rho

was originally

identified.

The

situa-

tion

is

changed

by expression

of the N

gene.

The

product

pN

is an

antitermination protein

that

acts

on both

of the immediate

early tran-

scription

units and

allows

RNA

polymerase

to

read

through

the

terminators

into

the delayed

early

genes

beyond them.

As for

other

phages,

still

another

control is

needed

to express

the late

genes

that

code for

the

components

of the

phage

particle.

This

switch is

regulated

by

gene

Q,

itself

one

of the

delayed

early

genes.

Its

product,

pQ,

is

another

antitermination

protein,

one

that

specifically

allows

RNA

polymerase

initiating

at

another

site,

the late

promoter

Pp,.

to read

through

a

terminator

that lies

between

it

and the

late

genes.

The

different

specificities

of

pN

andpe

estab-

lish

an important general

principle:

RNA

poly-

merase

interacts

with transcription

units in

such a

CHAPTER

L1 Transcriotion

way

that an ancillary

factlr

can splnslr

antitermi-

nation specifically

for

some transcripts. Termination

can

be controlled with

the same sort

of

preci-

sion as initiation.

Antitermi nation

Requi res

Sites That Are

Independent

of the Terminators

o

The

site where an

antiterminator

protein

acts

is

upstream of

the terminator site in

the

transcription

unit.

o

The location

of the antiterminator

site varies in

different

cases and can be in

the

oromoter or

within

the transcription unit.

Which

sites are involved in

controlling

the speci-

ficity

of antitermination?

The

antitermination

activity of

pN

is highly

specific,

b:ut the

antiter-

mination

event is not determined

by the

terminators

11

and

4p1;

the recognition

site needed

for

antitermi-

nation lies upstream

in the transcription

unit, that is,

at

a different

place

from

the terminator

site

at which

the action

eventually is accomplished.

FI€USI

ti"5$

shows

the locations

of the sites

required

for

antitermination

in

phage

lambda.

The recognition

sites required

for

pN

action

are called

nut

(f.or

N utilization).

The

sites

responsible

for

determining leftward

and right-

ward antitermination

are

described

as nutL

and

nutR, respectively.

Mapping

of

nut mutations

locates

nutL between

the startpoint

of P1 and

the beginning

of the N coding

region.

By

con-

trast, nutR

lies between

the end

of the

cro

gene

and

[1.

This

means that

the two

nut sites lie

in

different

positions

relative

to

the organization

of their

transcription

units.

Whereas

nutL is

near

the

promoter,

nutRis near

to the

termina-

tor.

(qut

is

different

yet

again, and

lies

within

the

promoter.)

How

does antitermination

occur?

When

pN

recognizes

the nut

site, it must

act

on RNA

polymerase

to ensure

that the

enzyme

can no

longer

respond

to the

terminator.

The

variable

Iocations

of.t]:re nut

sile s indicate

that

this

event

is linked

neither

to initiation

nor

to

termina-

tion,

but can

occur to RNA

polymerase

as it

elongates

the RNA

chain

past

the nut

site. As

illustrated

in FI6URE

11"54,

the

polymerase

then

becomes a

juggernaut

that continues past

the

terminator, hee

dless

of

its

signal.

(This

reaction

involves

antitermination

at rho-dependent

ter-

292

minators, but

pN

also suppresses

termination

at intrinsic terminators.

)

Is the ability of

pN

to

recognize

a short

sequence within

the transcription

unit an exam-

ple

of a more widely used mechanism for antiter-

mination?

Phages that

are

lambda

have different N

genes

and different antitermi-

nation

specificities.

The region

of

the

phage

genome

in

which

rlae nut

sites

lie has

a differ-

ent

sequence in each of these

phages,

and each

phage

must

therefore

have

characteristic

nut

sites

recognized specifically by its

own

pN.

Each

of these

pN products

must have the same

gen-

eral ability to

interact

with the transcription

apparatus in an antitermination capacity, but

also

have

a

different specificity for the sequence

of DNA that activates the

mechanism.

lrll,i.iliir

r.;,., i

Host RNA

potymerase

transcribes

[ambda

genes

and

termi-

nates

at

t sites.

pN

al.l.ows

it to

read through

terminators

in

the

L and

R1 units;

pQ

allows

it to

read through

the

R'terminator.

The sites

at which

pN

acts

(nut)

and

at which

pQ

acts

(qut)

are located

at different

relative

positions

in

the transcription

units.

irli:*i:rl.;i.:;.1, Ancitl"aryfactorsbindtoRNApolymeraseasitpassesthenut

site.

They

prevent

rho from

causing

termination

when the

potymerase reaches

the

terminator.

11.25

Termination and

Antitermination

Factors

Interact

with RNA

Potymerase

293

@

Termination

and

Antitermination

Factors Interact with

RNA

PoLymerase

.

Severa[

bacterial

proteins

are required for lambda

pN

to

interact with RNA

potymerase.

.

These oroteins are atso

invotved in

antitermination

in the

rn

operons of the

host

bacterium.

r

The lambda antiterminator

pQ

has a different

mode

of interaction that

involves

bindinq to

DNA at the

oromoter.

Termination and antitermination

are closely

connected

and involve bacterial and

phage pro-

teins that

interact with RNA

polymerase.

Sev-

eral

proteins

concerned with termination

have

been

identified by isolating mutants of E. coli

in

which

pN

is

ineffective.

Several of

these muta-

tions lie

in

the

rpoB

gele.

This argues that

pN

(like

rho factor)

interacts

with the

B

subunit of

the

core enzyme. Other

E

coli

mutations that

prevent pN

function identify rhe nusloci: nusA,

nusB, nusE,

and nusG.

(The

term

"nus"

is an

acronym

tor N utllization

substance.)

A

lambda nut site consists of two sequence

elements

called boxA and boxB.

Sequence ele-

ments

related to boxA are also

found in bacter-

ial operons. boxAis

required for binding bacterial

proteins

that are

necessary for antitermination

in both

phage

and bacterial operons. boxB

is

specific

to the

phage genome,

and mutations

in boxB

abolish the ability of

pN

to cause

antitermination.

Promoter

nut

site

Terminator

Factors

act on

RNA

polymerase

ii::a:-.i:

;

i.::1i,

Ancitlary

factors

bind to

RNA

potymerase

as

it

passes

certain

sites. The

nuf

site consists

of

two sequences. NusB-S10

joins

core enzyme

as it

passes

boxA.Ihen NusA

and

pN protein

bind as

potymerase

passes

boxB.

The

presence

of

pN

allows

the enzyme

to read

through the

termjnator,

pro-

ducing

a

joint

mRNA

that contajns immediate

earty sequences

joined

to

deLayed

earLy

sequences.

The

nus loci

code for

proteins

that form

part

of

the transcription

apparatus,

but that

are not

isolated

with

the RNA

polymerase

enzyme. The

nusA,

nusB,

and nusG functions

are concerned

solely

with the

termination

of transcription.

nusE

codes for

ribosomal

protein

S l0; the rela-

tionship

between its location

in

the l0S

sub-

unit and its function

in

termination

is not

clear.

The

Nus

proteins

bind to RNA

polymerase

ar

the nut

site, as

summarized

in

i:lf:i-:tiir

:

:.i,ij.

NusA is

a

general

transcription

factor

that

increases

the efficiency

of termination,

proba-

bly by

enhancing

RNA

polymerase's

tendency

to

pause

at terminators

(and

indeed

at other

regions

of secondary

structure;

see

below).

NusB

and S l0 form

a dimer that

binds

specifically

to

RNA

containing

a boxA seqtence.

NusG may

be concerned

with

the

general

assembly

of all

the

Nus

factors

into

a

complex

with RNA

polymerase.

Intrinsic

and rho-dependent

terminators

have

different

requirements

for the

Nus factors.

NusA is

required

for

termination

at intrinsic

ter-

minators,

and the reaction

can be

prevented

by

pN.

At

rho-dependent

terminators,

all four Nus

proteins

are

required,

and

again

pN

alone

can

inhibit

the

reaction.

The

common

feature

of

pN

at both

types

of terminator

is

to

prevent

the role

of

NusA in

termination.

Binding

of

pN

to

NusA

inhibits

the ability

of

NusA to

bind RNA, which

is

necessary

for

termination.

Antitermination

occurs in

the rrn

(rRNA)

d*1"#,#:1ift",',;:';lJl;ffi"}i#i

CHAPTER

11

Transcriotion

ognize these

sequences and

bind to RNA

poly-

merase

as it elongates

past

boxA. Ttiris

changes

the

properties

of

RNA

polymerase

in such

a way

that it can now

read through

rho-dependent

terminators

that are

present

within

the tran-

scription unit.

T}:re boxA

sequence of lambda

RNA

does not

bind NusB

-

S I 0

and

is

probably

enabled

to do so

by the

presence

of

NusA and

pN;

Ihe boxB

sequence

could be required

to stabilize

the reac-

tion. Thus variations

in boxA

sequences

may

determine which particular

set

of factors

is

required

for antitermination.

The

consequences

are the

same: when RNApolymerase passes

the

nut

sile, it is modified

by addition

of appropri-

ate factors

and fails to terminate

when

it sub-

sequently

encounters the

terminator

sites.

Antitermination

in

lambda requires pN

to

bind to RNA

polymerase

in

a manner

that

depends

on the

sequence of the

transcription

unit. Does

pN

recognizetl:'e

boxB site in

DNA

or

in the RNA

transcript? It

does not

bind inde-

pendently

to either

type of sequence,

but does

bind to a

transcription

complex

when

core

enzyme

passes

t]:re

boxB site.

pN

has

separate

domains that

recognizethe

boxB RNA

sequence

and

the NusA

protein.

After

joining

the tran-

scription

complex,

pN

remains

associated

with

the

core enzyme,

in effect

becoming

an addi-

tional subunit

whose

presence

changes

recog-

nition

of terminators. It

is

possible

that

pN

in

fact

continues

to bind to

both rhe

&oxB

RNA

sequence

and to RNA

polymerase,

which

main-

tains

a loop in

the RNA; thus

the role

of. boxB

RNA would

partly

be to

tether

pN

in the

vicin-

ity, effectively

increasing

its Iocal

concentration.

pQ,

which

prevents

termination

later

in

phage

infection

by acting

aI

qut,

has a

different

mode

of action. The

4rl

sequence

lies

at the

start

of the late

transcription

unit. The

upstream part

of

qut

lies

within

the

promoter,

whereas

the

downstream

part

lies

at the beginning

of the

transcribed

region.

This implies

that

pQ

action

involves

recognition

of DNA; it

also implies

that

its mechanism

of action, at least

concerning

the

initial

binding

to the complex,

musr

be

differ-

ent from

that

of

pN. pQ

interacts

with the

holoenzyme

during

the initiation

phase.

In fact,

o70 is required

for

the interaction

with

pe.

This

reinforces

the view

of RNA

polymerase

as an

interactive

structure

in

which conformational

changes

induced

at one

phase

may

affect

its

activity

at a later

phase.

The

basic

acrion of

pQ

is to interfere

with

pausing.

Once

pQ

has

acted

upon RNA

poly-

merase,

the enzyme

shows

much reducedpaus-

Terminator

CGCTCTTANNNNNNNNNAGCCCTGAAPuAAGGGCA

GCGAGAATNNNNNNNNNTCGGGACTTPvT

TCCC

GT

NusB-S10

NusG

DN

binds General

bind

to boxA

Facilitates

at boxB

termination

assembly

factor

of comolex

294

ing at all sites,

including rho-dependent

and

intrinsic terminators. This means that

pQ

does

not act directly on

terminatior'per

se, but

instead

allows the enzyme to

pass

the terminator more

quickly,

thus

depriving

the core

poiymerase

and/or accessory factor of the opportunity to

cause termination.

The

general principle

is

that

RNA

poly-

merase may exist in forms that are competent

to undertake

pailicular

stages of transcription,

and its activities at these stages can be changed

only

by modifying the appropriate form. Thus

substitutions of sigma

factors may

change

one

initiation-competent form into another; and

additions

of

Nus

factors may change the

prop-

erties of termination-competent

forms.

Termination seems to be closely connected

with

the mode of elongation.

In its

basic

tran-

scription

mode, core

polymerase

is subject to

many

pauses

during elongation, and

pausing

at a terminator

site is the

prerequisite

for ter-

mination

to occur. Under the influence of

fac-

tors such as NusA,

pausing

becomes

extended,

increasing

the efficiency of termination; while

under

the influence of

pN

or

pQ,

pausing

is

abbreviated,

decreasing the efficiency of termi-

nation.

Recognition sites for these factors are

found only

in

certain

transcription units, and as

a

result

pausing

and consequently termination

are altered only

in those units.

@

Summary

A transcription

unit comprises the DNA between

a

promoter,

where transcription

initiates, and

a terminator,

where it ends. One strand of

the

DNA in this region serves

as a template for syn-

thesis of a complementary

strand of

RNA. The

RNA-DNA

hybrid region is short and

transient,

as

the transcription

"bubble"

moves along

DNA.

The

RNA

polymerase

holoenzyme that

synthe-

sizes

bacterial

RNA

can

be separated into two

components.

Core enzyme is a

multimer of

structure

o2pB'that

is responsible for elongat-

ing the

RNA chain. Sigma

factor

(o)

is a single

subunit

that is required at the stage

of initia-

tion

for recognizing

the

promoter.

Core

enzyme

has

a

general

affinity for DNA.

The addition of sigma

factor reduces the

affin-

ity of

the enzyme

for nonspecific binding to

DNA,

but increases

its affinity for

promoters.

The rate at

which RNA

polymerase

finds its

pro-

moters

is too

great

to be accounted

for by dif-

fusion and

random contacts with

DNA; direct

exchange

of DNA sequences

heldby the enzyme

may be

involved.

Bacterial

promoters

are

identified

by

two

short conserved sequences

centered

at

-35

and

-10

relative to the

startpoint.

Most

promoters

have sequences

that

are well

sensus

sequences

at

these sites.

The distance

separating

the consensus

sequences

is l6 to

l8 bp. RNA

polymerase initially

"touches

dor,rm"

at the

-35

sequence

and then

extends

its con-

tacts over

the

-l

0

region.

The enzlrne

covers

-77

bp of

DNA. The

initial

"closed"

binary

complex

is converted to

an

"open"

binary

complex

by

melting of a sequence

of

-12

bp that

extends

from the

-10

region

to the

staftpoint.

The A-T-

rich base

pair

composition

of

the

-I0

sequence

may

be

important

for

the

melting

reaction.

The binary

complex

is converted

to

a ter-

nary complex by

the

incorporation

of ribonu-

cleotide

precursors. There

are

multiple

cycles

of

abortive

initiation,

during

which

RNA

poly-

merase synthesizes

and

releases

very short

RNA

chains without

moving

from the

promoter. At

the end of this

stage,

there

is a change

in struc-

ture, and

the core

enzyme

contracts

to cover

-50

bp. Sigma

factor

is either

released

Q0%

of'

cases)

or changes

its

form of

association

with

the core enzyme.

The core

enzyme

then

moves

along DNA,

synthesizing

RNA.

A locally

unwound

region of

DNA

moves

with

the

enzyme.

The enzyme

contracts

further

in size

to cover only

30

to

40 bp when

the

nascent

chain

has reached

I5 to

20

nucleotides;

then

it

continues

to

the end

of the

transcription

unit.

The

"strength"

of

a

promoter describes

the

frequency

at which

RNA

polymerase initiates

transcription;

it is

related to

the

closeness

with

which

its

-35

and

-i0

sequences

conform

to

the ideal consensus

sequences,

but

is influenced

also by

the sequences

immediately

downstream

of the startpoint.

Negative

supercoiling

increases

the strength

of certain

promoters. Transcription

generates

positive

supercoils

ahead

of

RNA

poly-

merase and

leaves

negative

supercoils

behind

the enzyme.

The core

enzyme

can be

directed

to

rec-

ognize

promoters

with different

consensus

sequences

by alternative

sigma

factors.

In

E. coli,

these sigma

factors

are

activated

by

adverse conditions,

such

as

heat shock

or

nitro-

gen

starvation.

B. subtilis

contains

a single

major

sigma

factor with

the

same

specificity

as the

E. coli sigma

factor and

also

contains

a variety

of minor

sigma

factors.

Another

series

of

fac-

tors

is

activated

when

sporulation

is initiated;

sporulation

is

regulated

by two

cascades

in

which

sigma

factor

replacements

occur

in the

forespore

and

mother

cell.

A

cascade

for

11.26

Summary

295

regulating

transcription

by substitution

of sigma

Refe

fe n

CgS

factors

is

also used

by

phage

SPOI.

The

geometry

of RNA

polymerase-promoter

recognition

is

similar for holoenzymes

contain-

ing

all

sigma factors

(except

o5a). Each

sigma

factor

causes RNA

polymerase

to initiate

tran-

scription

at a

promoter

that conforms

to a

par-

ticular

consensus

at-35

and-10.

Direct contacts

between

sigma

and DNA

at these

sites have

been demonstrated

for

E. coli

o70. The

o70

fac-

tor of E.

coli has

an N-terminal

autoinhibitory

domain

that

prevents

the DNA-binding

regions

from recognizing

DNA.

The autoinhibirory

region

is

displaced

by DNA

when the holoen-

zyme forms

an open complex.

Bacterial

RNA

polymerase

terminates

tran-

scription

at two

types

of sites. Intrinsic

termi-

nators

contain

a G-C-rich

hairpin

followed

by

a U-rich region.

They

are recognized

in vitro

by core

enzyme

alone. Rho-dependent

termi-

nators

require

rho factor

both

in vitro and in

vivo;

rho

binds

ro rut

siles that

are rich in

C and

poor

in

G residues

and that

precede

the actual site

of termination.

Rho is

a hexameric

ATp-

dependent

helicase

activity

that translocates

along

the RNA

until ir reaches

the RNA-DNA

hybrid

region

in

the transcription

bubble

of

RNA

polymerase,

where

it dissociates

the

RNA

from

DNA.

In both

types of

termination,

paus-

ing

by RNA

polymerase

is important

in

order

to allow

time for

the actual

termination

event

to occur.

The

Nus

factors

are required

for termination.

NusA is required

for intrinsic

terminators,

and

in

addition

NusB-Sl0

is

required

for rho-

dependent

terminators.

The

NusB-Sl0

dimer

recognizes

the boxA

sequence

of a n rzl

site in the

elongating

RNA;

NusA

joins

subsequently.

Antitermination

is

used

by some

phages

to

regulate progression

from

one

stage of

gene

expression

to the next.

The lambda gene

Ncodes

for

an antitermination protein

(pN)

that is nec-

essary to

allow RNA

poll'rnerase

to read through

the

terminators

located

at the

ends

of the imme-

diate early

genes.

Another

antitermination pro-

tein,

pQ,

is required

later

in

phage

infection.

pN

and

pQ

act

on RNA

polymerase

as it

passes

specific

sites

(nut

and

qut,

respecrively).

These

sites

are located

at

different

relative

positions

in

their respective

transcription

units.

pN

rec-

ognizes

RNA

polymerase

carrying

NusA

when

the enzyme passes

the sequence

boxB.

pN

then

binds

to the

complex

and

prevents

termination

by

antagonizing

the action

of

NusA

when

the

polymerase

reaches

the rho-dependent

terminator.

Transcription

Research

Transcription

0ccurs

by Base Pairing

in

a

"Bubble"

of Unoaired DNA

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Cold Spring Harbor

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299

The

Operon

I

CHAPTER

OUTLINE ]

Introductio

n

Regulation

Can Be Negative

or

Positive

r

In negative

regulation,

a repressor

protein

binds to an oper-

ator

to

prevent

a

gene

from

being

expressed.

o

In

posjtive

regulation,

a transcription

factor is required

to bind

at the

promoter

in

order to enabte

RNA

polymerase

to initiate

transcriotion.

StructuraI

Gene Clusters

Are

Coordinatety

Controtted

r

Genes

coding for

proteins

that function in

the

same

path-

way may

be located

adjacent

to one

another and

controtted

as a sing[e

unit

that is

transcribed into

a

potycistronic

mRNA.

The

/ac

Genes Are

Controlted

by a

Repressor

.

Transcription

of the IacZYA

gene

ctuster

is controtled

by

a

repressor protein

that binds

to an operator

that overlaps

the

promoter

at the

start of

the cluster.

r

The

repressor

protein

is a

tetramer

of

identical

subunits

coded

by the

gene

lacl.

The

lac 0peron

Can Be

Induced

o

Sma[[ molecules

that induce

an oDeron

are identical

with or

the substrate

for its

enzymes.

r

B-gatactosides

are the

substrates for

the enzymes

coded by

LocZYA.

.

In

the absence

of

B-galactosides,

the loc

operon is

expressed

on[y at a very

low

(basat)

tevel.

e

Addition

of specific

B-galactosides

induces

transcription

of

atl three

genes

of the operon.

c

The

lac mRNA

is

extreme[y

unstable;

as a result, induction

can be rapidly

reversed.

.

The

same

types

of systems

that

altow substrates

to induce

operons

coding

for metabotic

enzymes

can be used

to attow

end-products

to repress

the

operons

that code for

biosyn-

thetic

enzymes.

Repressor

Is

Controtted

by a Smat[-Motecute

Inducer

o

An inducer

functjons

by converting

the repressor

protein

into

a form

with

lower operator

affinity.

.

Repressor

has

two

binding sites.

one for

the operator

and

another for

the inducer.

r

Repressor

js

inactivated

by

an allosteric

interaction in

which

binding

of

inducer

at its

site changes

the

properties

of the

DNA-bindinq

site.

c6-Acting Constitutive Mutations Identifo

the

0perator

r

Mutations in the

operator cause constitutive

expression

of

a[[ three lac structural

genes.

r

These mutations

are os-acting and

affect only those

genes

on the contiguous stretch of DNA.

trans-Acting

Mutations

Identify

the Regulator

Gene

.

Mutations in

the /ocl

gene

are trans-acting

and affect

exDression

of alllocZYA ctusters in the

bacterium.

.

Mutations

that eliminate /acl function

cause constitutive

expression and are recessive.

r

Mutations

in the DNA-binding

site of the repressor

are

con-

stitutive because

the

repressor

cannot bind

the operator.

o

Mutations in

the

inducer-binding

site of the repressor

pre-

vent it from

being

inactivated

and cause

uninducibi[ity.

r

Mutations in

the

promoter

are un'inducibte

and crs-acting.

Multimeric

Proteins Have

Special Genetic Properties

r

Active repressor

is a tetramer

of

identicaI

subunits.

o

When mutant and

witd-type subunits are

present,

a singte

/ocf-d mutant subunit

can

inactivate

a tetramer

whose

other

subunits are witd-type.

t

locl-d mutations

occur

in

the DNA-binding

site. Their

effect

is exptained

by the

fact

that repressor

activity requires

at[

DNA-binding

sites in

the tetramer to be

active.

The

Repressor Monomer

Has SeveraI Domains

o

A singte repressor

subunit

can be divided into

the

N-terminaI DNA-binding

domajn.

a

hinge.

and

the core

of the orotein.

o

The DNA-binding

domain

contains two

short cx-hetical.

regions

that bind

the

major

groove

of DNA.

.

The inducer-binding

site

and the

regions

responsib[e

for

multimerization

are located in

the core.

Repressor Is

a

Tetramer

Made

of

Two

Dimers

o

Monomers

form a dimer

by making contacts

between

core

domains 1.

and 2.

r

Dimers form

a tetramer

bv interactions

between

the

o[igomerization hetices.

DNA-Binding

Is Regutated

by

an

Altosteric

Change

in Conformation

r

The DNA-binding

domain of

each

monomer

within

a dimer

inserts

into

the major

groove

of DNA.

@

''.'iN

300

Lewin Benjamin (ed.) Genes IX

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