Gen1 and Eme1 Play Redundant Roles in DNA Repair and Meiotic Recombination in Mice.
Gen1 and Eme1 Play Redundant Roles in DNA Repair and Meiotic Recombination in Mice.
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DOI：
10.1089/dna.2015.3022
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发表时间：
2016-10
影响因子：
3.1
通讯作者：
Xiaowen Wang;Herui Wang;Bin Guo;Ya Zhang;Yi-nv Gong;Chi Zhang;Hong Xu;Xiaohui Wu
中科院分区：
文献类型：
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作者：
Xiaowen Wang;Herui Wang;Bin Guo;Ya Zhang;Yi-nv Gong;Chi Zhang;Hong Xu;Xiaohui Wu
Holliday连接(HJ)的分辨对于同源重组和DNA修复是必不可少的。在酿酒酵母中，HJ分解酶Yen1和MUS81-Mms4复合体在DNA损伤修复中是冗余的。在培养的哺乳动物细胞中，Yen1同源基因1和MUS81-MMS1同源基因MUS81-EME1之间也存在这种冗余。在这份报告中，我们进一步测试了Gen1和EME1是否冗余地影响小鼠HJ相关的生理过程。我们发现，在早期胚胎阶段，Gen1和Eme1的纯合子突变会导致合成致死性。纯合子的Gen1突变不会导致小鼠胚胎成纤维细胞(MEF)的DNA修复缺陷，但使杂合的Eme1突变的MEF对各种DNA损伤剂更加敏感。基因1突变也降低了Eme1突变小鼠的减数分裂重组效率。这些结果表明，Gen1和Eme1在体内的DNA修复和减数分裂重组中发挥多余的作用。
Resolution of the Holliday junction (HJ) is essential for homologous recombination and DNA repair. In Saccharomyces cerevisiae, HJ resolvase Yen1 and the Mus81-Mms4 complex are redundant in DNA damage repair. In cultured mammalian cells, such redundancy also exists between Yen1 ortholog GEN1 and the Mus81-Mms1 ortholog MUS81-EME1. In this report, we further tested if GEN1 and EME1 redundantly affect HJ-related physiological processes in mice. We found that combined homozygous mutations of Gen1 and Eme1 led to synthetic lethality during early embryonic stages. Homozygous Gen1 mutations did not cause DNA repair deficiency in mouse embryonic fibroblast (MEF) cells, but made heterozygous Eme1 mutant MEFs more sensitive to various DNA-damaging reagents. Gen1 mutations also reduced the meiotic recombination efficiency in Eme1 mutant mice. These results suggest that Gen1 and Eme1 play redundant roles in DNA repair and meiotic recombination in vivo.