1月3日，国际著名杂志Cell Research在线刊登了中科院遗传与发育生物学研究所杨崇林研究组的最新研究成果“MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells，”，文章中，作者揭示了其在细胞凋亡及基因组稳定性研究中取得的新进展。
基因组稳定性对于真核生物的正常生长发育以及增殖是必不可少的前提条件。然而，在生存过程中，生物体基因组由于经常受到一些内在和外在因素的影响，造成各种形式的DNA损伤。为了保持基因组的稳定性，真核生物中已经形成了一种在进化上高度保守的机制，来修复应对各种DNA损伤。当DNA损伤严重到无法正确修复时，细胞会启动凋亡程序来避免受损细胞的大量增殖。维持基因组稳定性对于生物个体通过减数分裂将遗传信息准确地传递给子代是至关重要的。
中科院遗传与发育生物学研究所杨崇林研究组以秀丽线虫为模式，发现了一个对基因组稳定性维持起重要作用的基因mrg-1，其人类同源基因为Mrg15。在线虫mrg-1突变体的生殖腺中，细胞凋亡明显增多且可被DNA损伤修复和同源染色体联会的检查点基因的突变抑制。在mrg-1突变体的生殖腺细胞中，双链断裂DNA增多。在外源DNA损伤诱导后，mrg-1突变体生殖腺的终变期细胞发生高比例的染色体断裂。
研究还发现，在mrg-1的突变体性腺中，本应该呈现粗线期特征的细胞多停滞于细线期/偶线期，且这些细胞中组蛋白H3的第九位赖氨酸上的双甲基化（H3K9me2）的水平显著上调，这种表型与联会复合体组分的缺失突变体相似。这表明mrg-1的缺失使联会的正常进行受到了阻碍。此外，通过与本所程祝宽研究组的合作，他们发现在减数分裂的早期，mrg-1突变体中的同源染色体部分出现配对问题。这些结果表明，MRG-1通过促进DNA损伤的修复和同源染色体联会的正常进行，对基因组稳定性的维持发挥着重要作用。
博士研究生徐晶为该论文的第一作者。杨崇林博士为中国科学院“百人计划”入选者，其实验室的研究工作还受到国家自然科学基金以及科技部重大科学研究计划资助。（生物谷Bioon.com）
doi:10.1038/cr.2012.2
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MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells
Jing Xu, Xiaojuan Sun, Yudong Jing, Mo Wang, Kai Liu, Youli Jian, Mei Yang, Zhukuan Cheng and Chonglin Yang
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.
