MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells.
During meiotic cell division, proper chromosome synapsis and accurate repair of DNA double strand breaks (DSBs) are required to maintain genomic integrity, loss of which leads to apoptosis or meiotic defects. The mechanisms underlying meiotic chromosome synapsis, DSB repair and apoptosis are not fully understood. Here, we report that the chromodomain-containing protein MRG-1 is an important factor for genomic integrity in meiosis in Caenorhabditis elegans. Loss of mrg-1 function resulted in a significant increase in germ cell apoptosis that was partially inhibited by mutations affecting DNA damage checkpoint genes. Consistently, mrg-1 mutant germ lines exhibited SPO-11-generated DSBs and elevated exogenous DNA damage-induced chromosome fragmentation at diakinesis. In addition, the excessive apoptosis in mrg-1 mutants was partially suppressed by loss of the synapsis checkpoint gene pch-2, and a significant number of meiotic nuclei accumulated at the leptotene/zygotene stages with an elevated level of H3K9me2 on the chromatin, which was similarly observed in mutants deficient in the synaptonemal complex, suggesting that the proper progression of chromosome synapsis is likely impaired in the absence of mrg-1. Altogether, these findings suggest that MRG-1 is critical for genomic integrity by promoting meiotic DSB repair and synapsis progression in meiosis.
State Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Jing
J
Xu
Xiaojuan
X
Sun
Yudong
Y
Jing
Mo
M
Wang
Kai
K
Liu
Youli
Y
Jian
Mei
M
Yang
Zhukuan
Z
Cheng
Chonglin
C
Yang
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008540:Meiosis; D009154:Mutation; D034622:RNA Interference; D000099257:Meiotic Recombination Protein SPO11
D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D004706:Endodeoxyribonucleases; D006657:Histones; D000099257:Meiotic Recombination Protein SPO11; C470832:MRG-1 protein, C elegans