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:

The ObgE/CgtA GTPase influences the stringent response to amino acid starvation in Escherichia coli. Persky NS, Ferullo DJ, Cooper DL, Moore HR, Lovett ST. Mol Microbiol. 2009 Jun 23. [Epub ahead of print] [abstract]

A Role for Non-essential Domain II of Initiator Protein DnaA in Replication Control. Molt KL, Sutera VA, Moore KK, Lovett ST. Genetics. 2009 Jun 22. [Epub ahead of print] [abstract]

Reconstitution of initial steps of dsDNA break repair by the RecF pathway of E. coli. Handa N, Morimatsu K, Lovett ST, Kowalczykowski SC. Genes Dev. 2009 May 15;23(10):1234-45. [abstract]

Cell cycle synchronization of Escherichia coli using the stringent response, with fluorescence labeling assays for DNA content and replication. Ferullo DJ, Cooper DL, Moore HR, Lovett ST. Methods. 2009 May; 48(1):8-13. [abstract]

A DNA damage response in Escherichia coli involving the alternative sigma factor, RpoS. Merrikh H, Ferrazzoli AE, Bougdour A, Olivier-Mason A, Lovett ST. Proc Natl Acad Sci U S A. 2009. [abstract]

Mechanisms of Recombination: Lessons from E. coli. Persky NS, Lovett ST. Crit Rev Biochem Mol Biol. 2008;43(6):347-70. [abstract]

The stringent response and cell cycle arrest in Escherichia coli. Ferullo DJ, Lovett ST. Plos Genet. 2008;4(12):e1000300. [full text in PubMed Central] [abstract]

Lovett ST. Polymerase switching in DNA replication. Mol Cell. 2007;27(4):523-6. [abstract]

Foti JJ, Persky NS, Ferullo DJ, Lovett ST. Chromosome segregation control by Escherichia coli ObgE GTPase. Mol Microbiol. 2007;65(2):569-81. [abstract]

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. [abstract]

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. [abstract]

Lovett ST. Microbiology: Resurrecting a broken genome. Nature. 2006. [abstract]

Lovett ST. Replication arrest-stimulated recombination: Dependence on the RecA paralog, RadA/Sms and translesion polymerase, DinB. DNA Repair (Amst). 2006. [abstract]

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. [abstract]

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. [abstract]

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. [abstract]

Lovett ST. Filling the gaps in replication restart pathways. Mol Cell. 2005;17(6):751-2. [abstract]

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. [abstract]

View Complete Publication List on PubMed: Susan Lovett

 

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Last reviewed: July 17, 2009. E-mail comments or questions to the webmaster.