03/19/2024
By Irma Silva
The Kennedy College of Sciences, Department of Biological Sciences, invites you to attend a Master’s Thesis Defense by Deepshikha Ananthaswamy entitled: Investigating how the NuRD chromatin remodeler affects germline DSB repair in C. elegans.
Candidate: Deepshikha Ananthaswamy
Date: Friday, April 5, 2024
Time: 9 a.m to noon
Location: Olsen 353
Title: Investigating how the NuRD chromatin remodeler affects germline DSB repair in C. elegans
Committee members:
- Teresa Lee, Assistant Professor, University of Massachusetts Lowell
- Jessica Garb, Associate Professor, University of Massachusetts Lowell
- Peter Gaines, Chair, Professor, University of Massachusetts Lowell
Brief Abstract:
All cells encounter environmental hazards that damage DNA and generate toxic double stand breaks (DSBs). Therefore, organisms have evolved overlapping and redundant DSB repair pathways to protect genome integrity, particularly in germ cells. In response to DNA damaging agents like cisplatin and hydroxyurea, the Fanconi Anemia pathway helps repair DSBs. However, since genomic DNA is always packaged as chromatin, DSB repair must be coordinated with local chromatin remodeling. The Nucleosome Remodeling and Deacetylase (NuRD) complex is one complex that repositions nucleosomes, but its role in DSB repair remains unknown. In C. elegans, mutations in the catalytic subunit of NuRD, CHD4/LET-418, lead to defective DSB repair and sterility. let-418 mutants are highly sensitive to cisplatin and hydroxyurea in ways that phenocopy Fanconi Anemia pathway mutants: exposure to these DNA damaging agents causes reduced fertility, more DSBs, and severe chromosome fragmentation. We tested the genetic interaction between Fanconi Anemia mutant fcd-2 and NuRD mutant let-418, by assessing mitotic and meiotic DSB number, chromosome segregation, and embryonic survival. We find that let-418 is epistatic to fcd-2, indicating that it is necessary for proper germline DSB repair. Our results suggest that nucleosome remodeling mediated by NuRD has an important role in preventing DNA damage during oogenesis, demonstrating the importance of regulating local chromatin environment for maintaining genomic integrity.