Genomic integrity is a prerequisite for the survival, development and propagation of eukaryotic organisms. The genome is, however, frequently attacked by either endogenous or exogenous DNA damaging agents that generate a wide variety of DNA lesions. To maintain the integrity of their genomes, eukaryotic organisms have developed multiple evolutionarily conserved strategies to repair the lesions caused by DNA damaging insults. When DNA lesions are too severe to repair, cells are destined to undergo apoptosis so as to avoid their deleterious propagation. On the other hand, the maintenance of genomic integrity is required for faithful transmission of genetic information from parents to progeny through meiosis.
Using C.elegans as a model organism, scientists in Dr. Chonglin Yang’s group from the Institute of Genetics and Developmental Biology (IGDB), the Chinese Academy of Sciences found mrg-1, which is homologous to human Mrg15, plays an important role in maintenance of genomic integrity. 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 increased DSBs and were sensitive to DNA damage-induced chromosome fragmentation. 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. Moreover, through cooperation with Dr. Zhukuan Cheng’s group from IGDB, they found that in the early meiosis stage, some of mrg-1 mutants’ germline nuclei display defects in homologous chromosome pairing process. Altogether, these findings suggest that MRG-1 is critical for genomic integrity by promoting meiotic DSB repair and synapsis progression in meiosis.
This work with Dr. Jing Xu as the first author has been online published on Cell Research（DOI: 10.1038/cr.2012.2）. This research was supported by grants from the National Basic Research Program of China and the National Natural Science Foundation of China.
AUTHOR CONTACT:
Chonglin Yang, Ph.D.
Institute of Genetics and Developmetnal Biology, Chinese Academy of Sciences, Beijing, China.
(Image by Jing Xu etc.)
Figure. mrg-1 mutants are defective in progression of meiotic prophase. Representative images of DAPI-stained nuclei of whole-mount gonads from age-matched worms of the following strains are shown: (A and B) N2, (C and D) mrg-1(qa6200), (E and F) mrg-1(tm1227), (G and H) syp-2(ok307) and (I and J) brc-1(tm1145). Boxed regions in (A), (C), (E), (G), and (I) representing mid to late pachytene stages are magnified and shown in (B), (D), (F), (H), and (J), respectively. 319 gonads for each strain were analyzed. Bars, 10 μm.
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(Image by Jing Xu etc.)Figure. mrg-1 mutants are defective in progression of meiotic prophase. Representative images of DAPI-stained nuclei of whole-mount gonads from age-matched worms of the following strains are shown: (A and B) N2, (C and D) mrg-1(qa6200), (E and F) mrg-1(tm1227), (G and H) syp-2(ok307) and (I and J) brc-1(tm1145). Boxed regions in (A), (C), (E), (G), and (I) representing mid to late pachytene stages are magnified and shown in (B), (D), (F), (H), and (J), respectively. 319 gonads for each strain were analyzed. Bars, 10 μm.