The long term goal of the proposed research is to understand the rules governing recombination between repeated eukaryotic genes; the organism that will be used in these studies is the yeast Saccharomyces cerevisiae. This organism is particularly useful for the proposed studies since the development of the yeast transformation procedure allows construction of haploid yeast strains with duplicated copies of selectable genes. Five specific areas of research will be pursued. First, the properties of recombination between repeated genes located on non-homologous chromosomes will be analyzed. The frequency of such events will be examined as a function of the size and location of the repeated sequences. Second, the frequency of recombination between repeated sequences located on the same chromosome will be studies. These experiments will be done in the same genetic background and with the same repeated sequences as the studies involving non-homologous chromosomes; thus, a direct measurement of the relative frequency of these types of events can be made. Third, a genetic system will be developed to look for duplication of genes normally found in one copy per genome. Such events are likely to be important in understanding the origin of repeated gene families. Fourth, mutant strains will be isolated which have either higher or lower rates of recombination between repeated genes. Fifth, the properties of recombination involving transposable elements will be characterized. Since recombination between repeated genes on non-homologous chromosomes can result in translocations and since the activation of cellular onc genes in mammals is often associated with translocations, these studies may lead to insights into health-related problems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
7R01GM024110-12
Application #
3272067
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1988-08-01
Project End
1990-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Arts and Sciences
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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