susan lovettSusan T. Lovett, Ph.D.
Professor of Biology
Mechanisms of DNA repair and mutation avoidance

B.A., Cornell University
Ph.D., University of California, Berkeley

Contact Information

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 can provoke the accumulation of replication gaps by treatment with the chain-terminating drug, azidothymidine—we have identified and are studying several new repair factors that promote tolerance of the drug, as well as pathways that regulate them. We also investigate how cellular nutrition impacts the capacity for replication and repair, as well as structure of the bacterial chromosome.       

Mutational hotspots, exonucleases and mutation avoidance: A class of mutational hotspots occurs by misalignment of DNA strands during replication. We have studied chromosomal rearrangements that occur as a result of this aberrant replication and have found additional factors that may promote or inhibit such events. We have identified a potent mutational hotspot that promotes frequent switching between alterative replication templates. We are examining cis- and trans-acting factors, including exonucleases that control these “template-switch” hotspot mutations in E. coli.

Representative papers:

Insights into mutagenesis using Escherichia coli chromosomal lacZ strains that enable detection of a wide spectrum of mutational events.Seier T, Padgett DR, Zilberberg G, Sutera VA Jr, Toha N, Lovett ST. Genetics. 2011 Jun;188(2):247-62. [abstract]

Phenotypic landscape of a bacterial cell. Nichols RJ, Sen S, Choo YJ, Beltrao P, Zietek M, Chaba R, Lee S, Kazmierczak KM, Lee KJ, Wong A, Shales M, Lovett S, Winkler ME, Krogan NJ, Typas A, Gross CA. Cell. 2011 Jan 7;144(1):143-56. [abstract]

Toxicity and tolerance mechanisms for azidothymidine, a replication gap-promoting agent, in Escherichia coli. Cooper DL, Lovett ST. DNA Repair (Amst). 2011 Mar 7;10(3):260-70. [abstract]

Growth phase and (p)ppGpp control of IraD, a regulator of RpoS stability, in Escherichia coli. Merrikh H, Ferrazzoli AE, Lovett ST. J Bacteriol. 2009 Dec;191(24):7436-46. [abstract]

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 Jul;73(2):253-66. [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. [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]

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

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

RecA-independent recombination is efficient but limited by exonucleases. Dutra BE, Sutera VA, Jr., Lovett ST. Proc Natl Acad Sci U S A. 2007;104(1):216-21. [abstract]

The role of replication initiation control in promoting survival of replication fork damage. Sutera VA, Jr., Lovett ST. Mol Microbiol. 2006;60(1):229-39. [abstract]

Microbiology: Resurrecting a broken genome. Lovett ST. Nature. 2006.

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

RecJ exonuclease: substrates, products and interaction with SSB. Han ES, Cooper DL, Persky NS, Sutera VA, Jr., Whitaker RD, Montello ML, et al. Nucleic Acids Res. 2006;34(4):1084-91. [abstract]

DNA Repeat Rearrangements Mediated by DnaK-Dependent Replication Fork Repair. Goldfless SJ, Morag AS, Belisle KA, Sutera VA, Jr., Lovett ST. Mol Cell. 2006;21(5):595-604. [abstract]

Cis and trans-acting effects on a mutational hotspot involving a replication template switch. Dutra BE, Lovett ST. J Mol Biol. 2006;356(2):300-11. [abstract]

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

A bacterial G protein-mediated response to replication arrest. Foti JJ, Schienda J, Sutera VA, Jr., Lovett ST. Mol Cell. 2005;17(4):549-60. [abstract]

 

View Complete Publication List on PubMed: Susan Lovett

 


Last reviewed: Sept. 20, 2011. E-mail comments or questions to the webmaster.

 

 
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