All organisms must preserve the integrity of their genomes.
In humans, genetic instability is associated with cancer
and aging. Our laboratory seeks to understand the fundamental
mechanisms by which cells preserve genetic information by
the study of DNA damage repair and mutation avoidance in
the model organism Escherichia coli. In addition,
we have recently begun to ask how cell cycle events including
DNA replication and chromosome segregation are coupled to
cellular physiology and to the status of the chromosome.
We employ genetics, molecular biology, cell biology, and
biochemistry in the study of these pathways.
Replication fork repair and coordination with cell cycle:
Some of our studies in E. coli address the mechanism
of replication fork repair and its integration with the
bacterial cell cycle. We are particularly interested in
how recombination reactions are integrated and regulated
in the disassembly and reassembly of the replication fork,
how the organization of the chromosome influences fork repair
or whether the sensing of fork damage triggers control of
cell division, fork stabilization and replication initiation.
We have discovered a GTPase protein that may couple cell
division or chromosome segregation with events at the replication
fork and this protein is the subject of genetic and biochemical
analysis. We have also studied chromosomal rearrangements
that occur as a result of aberrant replication and have
found additional factors that may promote or inhibit such
events. We are currently characterizing the biochemical
and genetic properties of a new recombination factor, RadA,
which facilitates replication fork repair and mediates certain
chromosomal rearrangements. In reconstituted recombination
reactions in the test tube, we will test how RadA influences
these reactions.
Mutational hotspots, exonucleases and mutation avoidance:
The mismatch repair pathway contributes to replication fidelity
in all organisms. Our laboratory has defined the later stages
of the mechanism in E. coli by identification, purification
and characterization of the exonucleases that mediate the
excision of mismatched bases. Our studies also suggest that
the single-strand DNA exonucleases in E. coli abort
wide variety of strand mispairing events that lead to mutations
or genetic rearrangements. We have identified a potent mutational
hotspot that promotes frequent template-switching. We are
examining cis- and trans-acting factors that control these
hotspot mutations in E. coli.
Representative papers:
Goldfless, S., Segal-Morag, A., K. Belisle, V. A. Sutera,
Jr. and S. T. Lovett. 2006. DNA repeat rearrangements mediated
by DnaK-dependent replication fork repair. Mol. Cell 21:595-604.
[abstract]
Dutra, B. E. and S. T. Lovett. 2006. Cis- and trans-acting
effects on a mutational hotspot involving a replication
template switch. J. Mol. Biol. 356:300-311. [abstract]
Sutera, V. A. Jr. and S. T. Lovett. 2006. The role of replication
initiation control in survival of DNA damage. Mol. Microbiol
60:229-239. [abstract]
Lovett, S. T., 2006. Replication arrest stimulated recombination:
dependence on the RecA paralog, RadA/Sms and translesion
polymerase, DinB. DNA repair: in press. [abstract]
Han, E. S., D L. Cooper, N. S. Persky, V. A. Sutera, Jr.,
R. D. Whitaker, M. L. Montello and S. T. Lovett. 2006. RecJ
exonuclease: substrates, products and interaction with SSB.
Nuc. Acids Res. 34:1084-1091 [abstract]
Foti, J., J. Schienda, V. A. Sutera, Jr. and S. T. Lovett.
2005. A bacterial G-protein mediated response to replication
arrest. Mol. Cell 17: 549-560.[abstract]
Lovett, S. T. 2004. Encoded errors: mutations and rearrangements
mediated by misalignment at repetitive DNA sequences. Mol.
Microbiol. 52: 1243-1253. [abstract]
Lovett, S. T., R. L. Hurley, V. A. Sutera, Jr. R. H. Aubuchon
and M. A. Lebedeva.2002. Crossing-over between regions of
limited homology in Escherichia coli: RecA-dependent
and RecA-independent pathways. Genetics 160: 851-859. [abstract]
Beam, C. A., C. J. Saveson and S. T. Lovett. 2002. The
role of the radA/sms gene in recombination intermediate
processing in Escherichia coli. J. Bacteriol. 184:
6836-6844. [abstract]
Feschenko, V. V., L. A. Rajman and S. T. Lovett. 2003.
Stabilization of perfect and imperfect tandem repeats by
single-stranded DNA exonucleases. Proc. Natl. Acad. Sci.
USA 100: 1134-1139. [abstract]
Burdett, V., C. Baitinger, M. Viswanathan, S. T. Lovett,
P. Modrich. 2001. In vivo requirement for RecJ, ExoVII,
ExoI and ExoX in methyl-directed mismatch repair. Proc.
Nat. Acad. Sci. USA 98: 6765-6770.
Bzymek, M and S. T. Lovett. 2001. Evidence for two mechanisms
of palindrome-stimulated deletion in Escherichia coli:
single-strand annealing and replication slipped mispairing.
Genetics 158: 6765-6770. [abstract]
Viswanathan, M., V. Burdett, C. Baitinger, P. Modrich.
S. T. Lovett. 2001. Redundant exonuclease involvement in
Escherichia coli methyl-directed mismatch repair.
J. Biol. Chem:276:31053-31058. [abstract]
Viswanathan, M., J. J. Lacirignola, R. Hurley and S. T.
Lovett. 2000. A novel mutational hotspot in a natural quasipalindrome
in Escherichia coli. J. Mol. Biol. 302: 553-564.
[abstract]
View Complete Publication List on PubMed:
Susan Lovett
Last reviewed: August 23, 2006. E-mail
comments or questions to the webmaster.
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