Chromosome abnormalities due to meiotic errors are a leading cause of birth defects and spontaneous abortions in humans. The long-term objective of this work is to elucidate the mechanisms of meiotic pairing and to understand how these mechanisms help to ensure the fidelity of chromosome transmission from one generation to the next. A thorough mechanistic description of meiotic pairing has been hindered by the lack of appropriate in vivo tools. We have developed methods that allow the rapid capture and analysis of 3D images of chromosomal loci over time. Here we propose the use of these tools to measure the interaction kinetics between homologous and ectopic chromosomal loci. We will then explore how pairing interactions are affected by factors such as chromosome movement and compaction. Finally, we will identify structural features of the chromosome axis that limit non-specific chromosome interactions during meiosis. We will focus first on defining mechanisms by which Rec8, a structural component of the chromosome axis inhibits nonspecific chromosome interactions during meiosis. We will also carry out a mutant screen to identify other genes that suppress nonspecific pairing interactions. The results of these studies will lead to an understanding of the relationship between the structural features of chromosomes during meiosis and the forces that act upon them.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM075119-07
Application #
8446508
Study Section
Molecular Genetics A Study Section (MGA)
Program Officer
Janes, Daniel E
Project Start
2006-08-01
Project End
2016-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
7
Fiscal Year
2013
Total Cost
$282,805
Indirect Cost
$87,392
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Lui, Doris Y; Cahoon, Cori K; Burgess, Sean M (2013) Multiple opposing constraints govern chromosome interactions during meiosis. PLoS Genet 9:e1003197
Ho, Hsuan-Chung; Burgess, Sean M (2011) Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis. PLoS Genet 7:e1002351
Wu, Hsin-Yen; Ho, Hsuan-Chung; Burgess, Sean M (2010) Mek1 kinase governs outcomes of meiotic recombination and the checkpoint response. Curr Biol 20:1707-16
Lui, Doris; Burgess, Sean M (2009) Measurement of spatial proximity and accessibility of chromosomal loci in Saccharomyces cerevisiae using Cre/loxP site-specific recombination. Methods Mol Biol 557:55-63
Mell, Joshua Chang; Wienholz, Bethany L; Salem, Asmaa et al. (2008) Sites of recombination are local determinants of meiotic homolog pairing in Saccharomyces cerevisiae. Genetics 179:773-84
Mell, Joshua Chang; Komachi, Kelly; Hughes, Owen et al. (2008) Cooperative interactions between pairs of homologous chromatids during meiosis in Saccharomyces cerevisiae. Genetics 179:1125-7
Wu, Hsin-Yen; Burgess, Sean M (2006) Two distinct surveillance mechanisms monitor meiotic chromosome metabolism in budding yeast. Curr Biol 16:2473-9