PgmNr W4004: NuRD paralogs CHD-3/LET-418 promote meiotic double-stranded break repair In C. elegans .

Authors:
Carolyn Turcotte; Julia Rigothi; Erika Rosenkranse; Paula Checchi


Institutes
Marist College, Poughkeepsie, NY.


Keyword: Dosage compensation, cells, Meiosis Recombination

Abstract:

Normal meiotic progression requires that programmed double stranded breaks (DSBs) are induced on all chromosomes. This is significant, as unrepaired DSBs lead to defective gametes, which manifest in severe problems such as miscarriages and chromosomal disorders such as Down syndrome. Accordingly, DSBs must be faithfully repaired. This is accomplished by a series of conserved mechanisms which include ATP-dependent chromatin modifiers, proteins that epigenetically alter DNA. We have demonstrated a role for the nucleosome remodeling (NuRD) complex in DSB repair, wherein the Chromodomain helicase DNA binding protein CHD-3 and its paralog LET-418 promote normal meiotic progression and DSB repair in C. elegans. Loss of chd-3 alone results in a significantly decreased brood size, and these defects are exacerbated when combined with a loss-of-function let-418 allele. We discovered that the disruption of both paralogs also leads to chromosome fragmentation, which is indicative of faulty repair mechanisms. Using an antibody against the DSB marker RAD-51, we also found that DSBs abnormally persist in meiotic nuclei of let-418 mutant germ lines. We are currently generating several strains which will help us to further understand the molecular nature of these defects.  Taken together, these experiments will enable us to determine the role of the NuRD complex in the systematic repair of DSBs, which can be applied to other organisms such as humans.



Wormbase Genetic Index
1. chd-3
2. let-418