RRC ID 45533
Author Butuči M, Williams AB, Wong MM, Kramer B, Michael WM.
Title Zygotic Genome Activation Triggers Chromosome Damage and Checkpoint Signaling in C. elegans Primordial Germ Cells.
Journal Dev Cell
Abstract Recent findings have identified highly transcribed genes as a source of genome instability; however, the degree to which large-scale shifts in transcriptional activity cause DNA damage was not known. One example of a large-scale shift in transcriptional activity occurs during development, when maternal regulators are destroyed and zygotic genome activation (ZGA) occurs. Here, we show that ZGA triggers widespread chromosome damage in the primordial germ cells of the nematode C. elegans. We show that ZGA-induced DNA damage activates a checkpoint response, the damage is repaired by factors required for inter-sister homologous recombination, and topoisomerase II plays a role in generating the damage. These findings identify ZGA as a source of intrinsic genome instability in the germline and suggest that genome destabilization may be a general consequence of extreme shifts in cellular transcriptional load.
Volume 34(1)
Pages 85-95
Published 2015-7-6
DOI 10.1016/j.devcel.2015.04.019
PII S1534-5807(15)00283-X
PMID 26073019
MeSH Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Cell Cycle Checkpoints / genetics* DNA Damage / genetics* Genomic Instability / genetics* Germ Cells / cytology* Mutation / genetics Zygote / cytology*
IF 10.092
Times Cited 16
WOS Category DEVELOPMENTAL BIOLOGY CELL BIOLOGY
Resource
C.elegans tm1145