The Role of Chromosome Organization in DNA Double-Strand Break Repair

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dc.contributor.advisor Haber, James
dc.contributor.author Wang, Ruoxi
dc.date.accessioned 2016-05-12T19:07:50Z
dc.date.available 2016-05-12T19:07:50Z
dc.date.issued 2016
dc.identifier.uri http://hdl.handle.net/10192/32360
dc.description Joint BS/MS Program
dc.description.abstract 3D nuclear architecture is a key factor in regulating many cellular processes. Here, based on the published haploid yeast chromosome conformation capture data, we investigated the role of chromosome organization in DNA double-strand break repair, mainly through gene conversion. By using both single-donor viability assay and two-donor competition assay, we found the repair efficiency of a homologous donor sequence is highly correlated with their reconstituted distances to the recipient DSB site, which was deduced from the Hi-C database. Such correlation still exists when the break is induced at another locus. We also demonstrated that increasing the length of homology, inserting an ectopic Recombination Enhancer (RE), slowing down resection by FUN30 deletion, and enhancing RPA protein abundance effectively increased the repair efficiency. In addition, intra-chromosomal gene conversion is more frequent than inter-chromosomal events, but it is still constrained by chromosome organization. Our data revealed the tethering of centromeres to the spindle pole body during homologous recombination process, which agrees with the RabI configuration of yeast chromosomes. The result also provided extensive data to validate the chromosome polymer folding model. Through this study, we hope to provide more insights in the structural-functional correlation in eukaryotic genomes.
dc.description.sponsorship Brandeis University, Graduate School of Arts and Sciences, NIH Grant GM20056.
dc.format.mimetype application/pdf
dc.language English
dc.language.iso eng
dc.publisher Brandeis University
dc.relation.ispartofseries Brandeis University Theses and Dissertations
dc.rights Copyright by Ruoxi W. Wang 2016
dc.subject chromosome conformation
dc.subject double-strand break repair
dc.subject homology search
dc.subject homologous recombination
dc.title The Role of Chromosome Organization in DNA Double-Strand Break Repair
dc.type Thesis
dc.contributor.department Graduate Program in Molecular and Cell Biology
dc.degree.name MS
dc.degree.level Masters
dc.degree.discipline Molecular and Cell Biology
dc.degree.grantor Brandeis University, Graduate School of Arts and Sciences


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