Abstract
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.
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Acknowledgements
We thank the C. elegans Genetic Center (CGC) and Dr Shohei Mitani (Tokyo Women's Medical Univeristy, Japan) for providing worm deletion strains; Dr Xiaochen Wang (National Institute of Biological Sciences, China) for helpful suggestions and Dr Isabel Hanson for proofreading of the manuscript. This research was supported by grants from the National Basic Research Program of China (2011CB910102 and 2007CB947201) and the National Natural Science Foundation of China (31025015 and 30871266). CY is supported by the Hundred Talents Program of the Chinese Academy of Sciences.
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Xu, J., Sun, X., Jing, Y. et al. MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells. Cell Res 22, 886–902 (2012). https://doi.org/10.1038/cr.2012.2
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DOI: https://doi.org/10.1038/cr.2012.2
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