Recombination is important in the repair of broken DNA molecules, the generation of genetic diversity, and the correct segregation of chromosomes during formation of gametes. The goal of this study is to understand the mechanisms of meiotic recombination in the yeast Saccharomyces cerevisiae. Most of the proposed experiments are focused on the analysis of a chromosomal region with a very high level for meiotic recombination (recombination hotspot). This hotspot is located upstream of the HIS4 gene. Previous studies showed that the HIS4 hotspot has a high level of meiosis-specific double-strand DNA breaks (DSBs) and the activity of the hotspot requires the binding of several transcription factors. The first specific aim is to investigate the formation and processing of recombination intermediates at the HIS4 locus.
The second aim i s to examine the relationship between chromatin structure and meiotic recombination. The effect of yeast mutants that """"""""loosen"""""""" chromatin structure on hotspot activity will be studied. Long tracks of the repetitive DNA sequences of the form CCGNN (A nucleosome-excluding sequence) repress meiotic recombination, whereas shorter tracts of the same sequence elevate meiotic recombination. The third specific aim is to elucidate the mechanism by which nucleosome-excluding DNA sequences affect meiotic exchange. The fourth specific aim is to use the DNA microarray technology to map all of the strongest recombination hotspots in the yeast genome. The final specific aim is to identify the gene functions required to repair single stranded DNA loops; such loops can occur during meiotic recombination as a consequence of heteroduplex formation at a genetic locus heterozygous for an insertion or deletion.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM024110-25
Application #
6385313
Study Section
Genetics Study Section (GEN)
Program Officer
Anderson, Richard A
Project Start
1988-08-01
Project End
2003-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
25
Fiscal Year
2001
Total Cost
$360,243
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Moore, Anthony; Dominska, Margaret; Greenwell, Patricia et al. (2018) Genetic Control of Genomic Alterations Induced in Yeast by Interstitial Telomeric Sequences. Genetics 209:425-438
Kiktev, Denis A; Sheng, Ziwei; Lobachev, Kirill S et al. (2018) GC content elevates mutation and recombination rates in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 115:E7109-E7118
Zhang, Ke; Wu, Xue-Chang; Zheng, Dao-Qiong et al. (2017) Effects of Temperature on the Meiotic Recombination Landscape of the Yeast Saccharomyces cerevisiae. MBio 8:
Zhao, Ying; Dominska, Margaret; Petrova, Aleksandra et al. (2017) Properties of Mitotic and Meiotic Recombination in the Tandemly-Repeated CUP1 Gene Cluster in the Yeast Saccharomyces cerevisiae. Genetics 206:785-800
Omer, Sumita; Lavi, Bar; Mieczkowski, Piotr A et al. (2017) Whole Genome Sequence Analysis of Mutations Accumulated in rad27? Yeast Strains with Defects in the Processing of Okazaki Fragments Indicates Template-Switching Events. G3 (Bethesda) 7:3775-3787
Yin, Yi; Dominska, Margaret; Yim, Eunice et al. (2017) High-resolution mapping of heteroduplex DNA formed during UV-induced and spontaneous mitotic recombination events in yeast. Elife 6:
Zheng, Dao-Qiong; Zhang, Ke; Wu, Xue-Chang et al. (2016) Global analysis of genomic instability caused by DNA replication stress in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 113:E8114-E8121
Andersen, Sabrina L; Zhang, Aimee; Dominska, Margaret et al. (2016) High-Resolution Mapping of Homologous Recombination Events in rad3 Hyper-Recombination Mutants in Yeast. PLoS Genet 12:e1005938
O'Connell, Karen; Jinks-Robertson, Sue; Petes, Thomas D (2015) Elevated Genome-Wide Instability in Yeast Mutants Lacking RNase H Activity. Genetics 201:963-75
Yin, Yi; Petes, Thomas D (2015) Recombination between homologous chromosomes induced by unrepaired UV-generated DNA damage requires Mus81p and is suppressed by Mms2p. PLoS Genet 11:e1005026

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