Progress has been made in the following areas: 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 substrate requirements of proteins that form DSBs, and the factors that control their location, frequency and timing. Current research is directed at determining the chromosome structural elements that determine where DSBs do and do not form. We applied microarray-based whole genome analysis to recombination intermediate distributions, and have recently shown that the DSBs that initiate meiotic recombination are distributed much more evenly had been previously believed. 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. Recent experiments have identified the interplay between meiosis-specific chromosomal proteins and the Sgs1 helicase (the budding yeast homolog of the helicase mutated in Bloom's syndrome) as playing a critical role in controlling crossover formation. Other experiments have identified the cyclin-dependent cell cycle kinase, Cdc28, as controlling the meiotic transition between recombination intermediates and mature crossover products. 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 single DSB induces phosphorylation of histone H2A by the yeast ATM and ATR homologs in a large region of chromatin (> 40 kb). This chromatin modification is necessary for the post-replicative recruitment of cohesin to broken chrommosomes. Current research is aimed at examining similar events in meiosis.
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