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.
Project Narrative Human reproductive health can be compromised by exposure to myriad compounds found in prescription drugs, food containers and toxic waste products found in the environment. This work is significant because it will identify genetic and biochemical pathways that may be direct targets of these insults during gametogenesis. A detailed understanding of these pathways will aid in identifying the underlying causes of human infertility and birth defects by exposure to environmental contaminants.
|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|