Biology Reference
In-Depth Information
problems (reviewed in Ref.
1
). It has been suggested that NusA may be
involved in a form of TCR that is independent of
Mfd
and can account for
the mild effect of
mfd
mutations;
58,59
however, there is as yet no direct
biochemical evidence for TCR in the absence of
Mfd
. Furthermore, the
biological response (MFD) that reflects TCR and was the basis for the subse-
quent identification of
Mfd
is absent when the protein is not active. In
Bacillus
subtilis
,
Mfd
has been implicated in recombination,
70
and in both
B. subtilis
71
and
Campylobacter jejuni
,
72
it has been reported to have a mutagenic effect. In
addition,
Mfd
has been reported to release ECs arrested by the bacteriophage
HK022 Nun protein.
73
Until the biochemical bases for these observations are
known, interpreting an
Mfd
-dependent biological response as TCR without
direct measurements of repair is of questionable validity.
Note added in proof
: In contrast to data implicating TCR in the repair of
oxidative lesions, Schalow
et al.
(J. Bacteriol. 2012;194: 2637-2645) have
reported that neither
mfd
nor uvrA mutations affect the survival, the rate of
recovery of transcription, or the rate of removal of formamidopyrimidine DNA
glycosylase sensitive sites in the DNA of actively growing
E. coli
treated with
H
2
O
2
, consistent with the idea that neither TCR nor GGR contribute signifi-
cantly to the repair of oxidative lesions produced by this compound.
In addition, Deaconescue
et al.
(
Proc Nat Acad Sci USA
2012;
:3353-
3358) recently published studies of the structure of
Mfd
, providing more details
about the interaction of
Mfd
with
UvrA
and the conformational changes the
protein undergoes during its interactions with other components of TCR. Their
data, like those of Manelyte
et al.
,
39
indicate that
Mfd
can dissociate a stalled
EC without interacting with
UvrA
; they propose that the likely sequence of
events in TCR is the interaction of
Mfd
with a stalled EC by protein-protein
contacts and the dissociation of the EC prior to the recruitment of
UvrA
.
109
Acknowledgments
Support for our research on TCR for many years was provided by grants from the National
Cancer Institute, NIH 5R35 CA44349, RO1 CA91456, and RO1 CA90915. Current support is
provided from grant 1RO1 ES0188344 from the National Institute of Environmental Health
Sciences, NIH.
References
1. Hanawalt PC, Spivak G. Transcription-coupled DNA repair: two decades of progress and
surprises.
Nat Rev Mol Cell Biol
2008;
:958-70.
2. Witkin EM. Radiation-induced mutations and their repair.
Science
1966;
9
:1345-52.
3. Zolan ME, Cortopassi GA, Smith CA, Hanawalt PC. Deficient repair of chemical adducts in
alpha DNA of monkey cells.
Cell
1982;
152
:613-9.
28