Our research examines the molecular mechanism of recombination and DNA damage repair in the yeast Saccharomyces cerevisiae. Our primary focus is on meiotic recombination, but we also study events that occur during vegetative growth. Current research involves three aspects of these complex biological processes: Initiation of meiotic recombination: Meiotic recombination is initiated by DNA double-strand breaks (DSBs); both the location and timing of break formation is tightly controlled.
Our aim i s to determine the proteins that form DSBs, their substrate requirements, and the factors that control their location, frequency and timing. Current research is directed at determining the composition of the protein complex that catalyzes DSB formation and at determining the chromosome structural elements that determine where DSBs do and do not form. Mechanism of meiotic recombination: We have developed techniques to isolate and characterize unstable intermediates in meiotic recombination, and have used these techniques to demonstrate that the two classes of meiotic recombination (events associated with crossing-over versus events not accompanied by crossing-over) proceed by distinct molecular mechanisms. Our current aim is to determine the repair proteins that participate in both pathways, that are unique to one or the other pathway, and that determine the choice between crossover and noncrossover recombination. Chromatin modification and double-strand break repair: We are examining changes in chromatin structure and modification that occur in response to DNA double-strand breaks, using as a model system a single DSB formed by the HO endonuclease in vegetative cells. We have shown that a large region of chromatin (> 40 kb) is modified, by phosphorylation of histone H2A, in response to this defined DSB. Current research is aimed at determining the proteins responsible for this DSB-associated chromatin modification and remodeling, and at examining similar events in meiosis.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005268-17
Application #
7038486
Study Section
(LB)
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Nakamura, Asako; Sedelnikova, Olga A; Redon, Christophe et al. (2006) Techniques for gamma-H2AX detection. Methods Enzymol 409:236-50
Jessop, Lea; Allers, Thorsten; Lichten, Michael (2005) Infrequent co-conversion of markers flanking a meiotic recombination initiation site in Saccharomyces cerevisiae. Genetics 169:1353-67
Lichten, Michael (2005) Rad50 connects by hook or by crook. Nat Struct Mol Biol 12:392-3
Borde, Valerie; Lin, Waka; Novikov, Eugene et al. (2004) Association of Mre11p with double-strand break sites during yeast meiosis. Mol Cell 13:389-401
Schlecht, Helene B; Lichten, Michael; Goldman, Alastair S H (2004) Compartmentalization of the yeast meiotic nucleus revealed by analysis of ectopic recombination. Genetics 168:1189-203
Shroff, Robert; Arbel-Eden, Ayelet; Pilch, Duane et al. (2004) Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr Biol 14:1703-11
Unal, Elcin; Arbel-Eden, Ayelet; Sattler, Ulrike et al. (2004) DNA damage response pathway uses histone modification to assemble a double-strand break-specific cohesin domain. Mol Cell 16:991-1002
Borde, V; Goldman, A S; Lichten, M (2000) Direct coupling between meiotic DNA replication and recombination initiation. Science 290:806-9
Allers, T; Lichten, M (2000) A method for preparing genomic DNA that restrains branch migration of Holliday junctions. Nucleic Acids Res 28:e6
Gerton, J L; DeRisi, J; Shroff, R et al. (2000) Inaugural article: global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 97:11383-90

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