05/11/2023
By Irma Silva
The Kennedy College of Science, Department of Biological Sciences, invites you to attend a M.S. thesis proposal defense by Deepshikha Ananthaswamy entitled “Investigating how the NuRD chromatin remodeler affects germline DSB repair in C. elegans.”
Candidate: Deepshikha Ananthaswamy
Date: Tuesday, May 23, 2023
Time: noon to 3 p.m.
Location: Ball Hall 302
Committee Members:
- Teresa Lee, Assistant Professor, Biological Sciences, University of Massachusetts Lowell
- Jessica Garb, Associate Professor, Biological Sciences, University of Massachusetts Lowell
- Peter Gaines, Professor, Biological Sciences, University of Massachusetts Lowell
Brief Abstract:
All cells encounter stress that cause toxic DNA damage like double strand breaks (DSBs), so organisms have evolved multiple overlapping DSB repair pathways to maintain genome integrity. Full DSB repair in germ cells is particularly important, because any remaining genomic damage will cause deleterious mutations for the next generation. DSB repair must function within the context of local chromatin landscapes, including nucleosome positioning. However, the role nucleosome remodeling during meiotic DSB repair remains poorly understood.
Mutations in LET-418/CHD4, the catalytic subunit of the nucleosome remodeling and deacetylase complex (NuRD), cause defects in DSB repair, affecting embryonic survival and overall fertility. These defects worsen when let-418 mutants are challenged with exogenous DSBs from cisplatin or hydroxyurea. The excess number of mitotic DSBs and persistent recombination intermediates observed in let-418 mutants phenocopies what occurs in Fanconi anemia (FA) pathway mutants. We are currently exploring the genetic relationship between NuRD components and the FA pathway. These data will define a role for NuRD during germline DSB repair and determine whether nucleosome remodeling is required to generate an accessible chromatin environment for proper DSB resolution.