section 26.3
Gene Regulation in Eukaryotes
599
protein and enables
E. coli
RNA polymerase to ignore
certain transcription termination sites and thereby extend
synthesis of these mRNAs. It acts together with a bacte-
rial protein, NusA, by binding to a site called nutR in the
k
DNA. When RNA polymerase, which has initiated tran-
scription at pR, reaches this site, it picks up the N-NusA
complex and is thereby modified such that it is able to
ignore the tRl and tR2 terminators. A similar site,
nutL,
is present downstream from the pL promoter. Because of
this antitermination effect, in time RI is extended until
the DNA replication proteins and another regulatory pro-
tein, Q, are made. Q is also an antitermination protein. A
small constitutively synthesized RNA, R4, is made from
the outset of the infection. The Q protein binds to a site
(qut)
downstream from the promoter for R4, causing RNA
polymerase to antiterminate, and R4 is extended to form an
mRNA that encodes the head, tail, and lysis proteins. From
the extended Rl mRNA, the gene-Cro protein is made. The
concentration of Cro ultimately reaches a value at which
the protein dimerizes, producing the active form. The Cro
dimer acts as a repressor at both pL and pR; this activ-
ity turns off synthesis of early proteins that are no longer
needed and prevents excess synthesis of DNA replication
proteins.
Lambda, like many phages (but not T4 or T7), can
engage in two alternative life cycles. In the
lytic cycle,
progeny phage particles are produced and the cell ul-
timately lyses, releasing the phage to the surrounding
medium. In the
lysogenic cycle,
injected phage DNA is
repressed and becomes inserted into the bacterial chromo-
some. At a later time, if the bacterial DNA is damaged
sufficiently, the phage DNA is excised and a lytic cycle
ensues. DNA damage, in a complicated way, leads indi-
rectly to inactivation of the cell repressor and subsequent
excision of the phage DNA and production of progeny
phage. The
int
gene (Figure 26-6) encodes the enzyme
that causes insertion of the phage DNA into the bacterial
chromosome. Neither the cl repressor nor the Int protein
is needed in the lytic cycle; however, and both are needed
in the lysogenic cycle and are coordinately regulated. The
two products, Cl and Int, are encoded in different mRNA
molecules but synthesis of the mRNA is initiated by a
common signal. The product of the gene
ell
is a positive
regulatory element. Like the cAMP-CRP complex in the
lac operon, the
ell
product must be bound to the DNA
adjacent to the promoters for the mRNAs encoding the
cl and Int proteins. In this way, the choice of the lytic
versus the lysogenic cycle depends on the concentration
of the ell protein. If the concentration is low, neither cl
repressor nor Int is made and the lytic cycle is followed;
if the concentration is high, both cl repressor and Int are
made and the lysogenic cycle occurs. The concentration
of ell protein is regulated in response to environmental
influences.
Regulons
One fairly well-studied regulon is the
heat-shock
or
high-
temperature protection regulon (htp)
which synthesizes
a variety of proteins when bacteria are exposed to temper-
atures above 40°C. In
E. coli
, a single protein, the product
of the
htpR
gene, is a positive effector of all mRNAs of the
regulon. The C-terminal end of the HtpR protein is homol-
ogous to the RNA polymerase
o
subunit, which suggests
that the heat-shock response involves a reprogramming of
RNA polymerase by this
a
-like protein, enabling RNA
polymerase to initiate transcription at a class of promoters
that is not otherwise recognized.
The inducible SOS repair system was described in
Chapter 24. This system allows the frequency of repli-
cation errors to increase when repair is necessary and is
regulated in order to keep the normal error frequency low.
Since the repair system is needed only following certain
types of DNA damage, some feature of the damage may
act as the inducer. Several genes representing functions
not directly related to repair are also components of this
system, which is called the
SOS regulon.
Common to all
mRNAs of the SOS regulon is an operator region to which
a repressor,
LexA,
binds. When DNA is damaged, a pro-
tein called RecA binds to the damaged segment. Binding
causes a conformational change in the protein and converts
it to a specific protease that is active against only a small
number of repressor proteins, LexA among them. Cleav-
age of LexA prevents it from binding to the SOS operator,
so transcription of all mRNAs of the SOS regulon occurs,
yielding Uvr enzymes, RecA, and SOS repair proteins.
LexA normally represses its own synthesis (it is autoreg-
ulated). However, the large amount of RecA protein made
after the LexA protein has been cleaved continues to be
activated for proteolysis and cleaves LexA; thus, all pro-
teins of the SOS regulon continue to be made. Once DNA
repair is completed, RecA loses its proteolysis activity,
and LexA is no longer cleaved. Without RecA protease
activity, newly made LexA rapidly accumulates, binds to
the SOS operators, and turns off the SOS regulon; thus,
the state of the cell existing before DNA damage occurred
is reestablished.
26.3 Gene Regulation in Eukaryotes
Regulationof gene expression in eukaryotes proceeds pri-
marily by control of transcription as in prokaryotes.
Some systems are also regulated at the translational level.
