title: Zygotic Genome Activation Triggers Chromosome Damage and Checkpoint Signaling in C. elegans Primordial Germ Cells.
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.
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Melina
authors.initials: M
authors.lastname: Butuči
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Williams
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Wong
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Brendan
authors.initials: B
authors.lastname: Kramer
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: mattm@usc.edu.
authors.forename: W Matthew
authors.initials: WM
authors.lastname: Michael
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D005854:Germ Cells / Q000166:cytology*; D009154:Mutation / Q000235:genetics; D015053:Zygote / Q000166:cytology*
chemical_list: D029742:Caenorhabditis elegans Proteins