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:
Merrikh H, Ferrazzoli AE, Bougdour A, Olivier-Mason A, Lovett ST. A DNA damage response in Escherichia coli involving the alternative sigma factor, RpoS. Proc Natl Acad Sci U S A. 2009.
Persky NS, Lovett ST. Mechanisms of Recombination: Lessons from E. coli. Crit Rev Biochem Mol Biol. 2008;43(6):347-70.
Ferullo DJ, Lovett ST. The stringent response and cell cycle arrest in Escherichia coli. Plos Genet. 2008;4(12):e1000300. [full text in PubMed Central]
Lovett ST. Polymerase switching in DNA replication. Mol Cell. 2007;27(4):523-6.
Foti JJ, Persky NS, Ferullo DJ, Lovett ST. Chromosome segregation control by Escherichia coli ObgE GTPase. Mol Microbiol. 2007;65(2):569-81.
Dutra BE, Sutera VA, Jr., Lovett ST. RecA-independent recombination is efficient but limited by exonucleases. Proc Natl Acad Sci U S A. 2007;104(1):216-21.
Sutera VA, Jr., Lovett ST. The role of replication initiation control in promoting survival of replication fork damage. Mol Microbiol. 2006;60(1):229-39.
Lovett ST. Microbiology: Resurrecting a broken genome. Nature. 2006.
Lovett ST. Replication arrest-stimulated recombination: Dependence on the RecA paralog, RadA/Sms and translesion polymerase, DinB. DNA Repair (Amst). 2006.
Han ES, Cooper DL, Persky NS, Sutera VA, Jr., Whitaker RD, Montello ML, et al. RecJ exonuclease: substrates, products and interaction with SSB. Nucleic Acids Res. 2006;34(4):1084-91.
Goldfless SJ, Morag AS, Belisle KA, Sutera VA, Jr., Lovett ST. DNA Repeat Rearrangements Mediated by DnaK-Dependent Replication Fork Repair. Mol Cell. 2006;21(5):595-604.
Dutra BE, Lovett ST. Cis and trans-acting effects on a mutational hotspot involving a replication template switch. J Mol Biol. 2006;356(2):300-11.
Lovett ST. Filling the gaps in replication restart pathways. Mol Cell. 2005;17(6):751-2.
Foti JJ, Schienda J, Sutera VA, Jr., Lovett ST. A bacterial G protein-mediated response to replication arrest. Mol Cell. 2005;17(4):549-60.
View Complete Publication List on PubMed:
Susan Lovett
Last reviewed: Feb 6, 2009. E-mail
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