PgmNr W4003: NuRD Chromatin Remodelers Block Checkpoint Activation in the C. elegans Germ Line.

Authors:
Sol Sloat; Julia Rigothi; Carolyn Turcotte; Nicolas Andrews; Paula Checchi


Institutes
Marist College, Poughkeepsie, MY.


Keyword: Dosage compensation, cells, Meiosis Recombination

Abstract:

In order to form viable gametes, double stranded breaks (DSBs) must be induced and correctly repaired during meiotic prophase I. Failure to correctly repair DSBs can result in defective gametes, which in humans, results in infertility, miscarriage, or chromosome disorders.  We have found that in C. elegans, timely DSB repair is mediated by the  Nucleosome Remodeling Deacetylase (NuRD) complex.  Mutations in the genes encoding Chromodomain helicase DNA binding protein CHD-3 and its paralog LET-418 result in persisting DSBs and chromosome fragmentation that are coincident with increased germline apoptosis.   Here, we investigate the genetic, cellular and molecular role of the NuRD chromatin remodeling complex and its relationship with meiotic checkpoint signaling in the C. elegans germ line.  As in other organisms, checkpoint kinase 1 (CHK-1) is responsible for coordination of the DNA damage response (DDR) that leads to either cell cycle arrest, DNA repair, or apoptosis. We found that let-418 mutants had higher levels of phosphorylated CHK-1 protein (pCHK-1) than wild type controls. These data are corroborated by cellular evidence in which pCHK-1 foci are detected in let-418 germ cells using antibody staining, as well as genetic evidence demonstrating that knockdown of chk-1 as well as its downstream effector cep-1(p53) suppress apoptosis in let-418 mutants.  Taken together, these results support a model wherein the NuRD complex machinery ensures error-free gamete formation by inhibiting meiotic checkpoints.



Wormbase Genetic Index
1. let-418