REC-1 and HIM-5 distribute meiotic crossovers and function redundantly in meiotic double-strand break formation in Caenorhabditis elegans.
REC-1 and HIM-5 distribute meiotic crossovers and function redundantly in meiotic double-strand break formation in Caenorhabditis elegans.
复制标题
REC-1和HIM-5在秀丽隐杆线虫中的减数分裂双链断裂中分发减数分裂跨界和功能。
DOI：
10.1101/gad.266056.115
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发表时间：
2015-09-15
影响因子：
10.5
通讯作者：
Boulton SJ
中科院分区：
文献类型：
--
作者：
Chung G;Rose AM;Petalcorin MI;Martin JS;Kessler Z;Sanchez-Pulido L;Ponting CP;Yanowitz JL;Boulton SJ
在这项研究中，Chung等人使用全基因组测序来证明rec-1编码HIM-5的一个远缘同源物。他们还表明，REC-1在体外被CDK磷酸化，REC-1中CDK共有位点的突变损害了体内减数分裂交叉分布。这些发现提供了新的见解减数分裂DSB的形成和交叉定位。秀丽隐杆线虫基因rec-1是在后生动物中发现的第一个影响减数分裂交换沿着染色体分布的遗传位点。我们报告说，rec-1编码HIM-5的一个远缘同源物，这是通过全基因组测序发现的，并通过多个基因组编辑的等位基因证实。REC-1在体外被细胞周期蛋白依赖性激酶（CDK）磷酸化，REC-1中CDK共有位点的突变会影响体内减数分裂的交叉分布。出乎意料的是，rec-1; him-5双突变体由于减数分裂双链断裂形成缺陷而具有合成致死性。因此，我们发现了对减数分裂DSB形成和交叉定位的意想不到的稳健性，其由HIM-5和REC-1执行并由磷酸化调节。
In this study, Chung et al. use whole-genome sequencing to demonstrate that rec-1 encodes a distant paralog of HIM-5. They also show that REC-1 is phosphorylated by CDK in vitro, and mutation of the CDK consensus sites in REC-1 compromises meiotic crossover distribution in vivo. These findings provide new insights into meiotic DSB formation and crossover positioning. The Caenorhabditis elegans gene rec-1 was the first genetic locus identified in metazoa to affect the distribution of meiotic crossovers along the chromosome. We report that rec-1 encodes a distant paralog of HIM-5, which was discovered by whole-genome sequencing and confirmed by multiple genome-edited alleles. REC-1 is phosphorylated by cyclin-dependent kinase (CDK) in vitro, and mutation of the CDK consensus sites in REC-1 compromises meiotic crossover distribution in vivo. Unexpectedly, rec-1; him-5 double mutants are synthetic-lethal due to a defect in meiotic double-strand break formation. Thus, we uncovered an unexpected robustness to meiotic DSB formation and crossover positioning that is executed by HIM-5 and REC-1 and regulated by phosphorylation.