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首页> 外文期刊>Development >The CRL2LRR-1 ubiquitin ligase regulates cell cycle progression during C. elegans development.
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The CRL2LRR-1 ubiquitin ligase regulates cell cycle progression during C. elegans development.

机译：CRL2LRR-1泛素连接酶在秀丽隐杆线虫发育过程中调节细胞周期进程。

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摘要

The molecular mechanisms that regulate cell cycle progression in a developmental context are poorly understood. Here, we show that the leucine-rich repeat protein LRR-1 promotes cell cycle progression during C. elegans development, both in the germ line and in the early embryo. Our results indicate that LRR-1 acts as a nuclear substrate-recognition subunit of a Cullin 2-RING E3 ligase complex (CRL2(LRR-1)), which ensures DNA replication integrity. LRR-1 contains a typical BC/Cul-2 box and binds CRL2 components in vitro and in vivo in a BC/Cul-2 box-dependent manner. Loss of lrr-1 function causes cell cycle arrest in the mitotic region of the germ line, resulting in sterility due to the depletion of germ cells. Inactivation of the DNA replication checkpoint signaling components ATL-1 and CHK-1 suppresses this cell cycle arrest and, remarkably, restores lrr-1 mutant fertility. Likewise, in the early embryo, loss of lrr-1 function induces CHK-1 phosphorylation and a severe cell cycle delay in P lineage division, causing embryonic lethality. Checkpoint activation is not constitutive in lrr-1 mutants but is induced by DNA damage, which may arise due to re-replication of some regions of the genome as evidenced by the accumulation of single-stranded DNA-replication protein A (ssDNA-RPA-1) nuclear foci and the increase in germ cell ploidy in lrr-1 and lrr-1; atl-1 double mutants, respectively. Collectively, these observations highlight a crucial function of the CRL2(LRR-1) complex in genome stability via maintenance of DNA replication integrity during C. elegans development.
机译：在发育背景下调节细胞周期进程的分子机制了解甚少。在这里，我们表明，富含亮氨酸的重复蛋白LRR-1可以在秀丽隐杆线虫发育过程中在种系和早期胚胎中促进细胞周期进程。我们的结果表明LRR-1充当Cullin 2-RING E3连接酶复合物（CRL2（LRR-1））的核底物识别亚基，可确保DNA复制的完整性。 LRR-1包含一个典型的BC / Cul-2盒，并在体外和体内以BC / Cul-2盒依赖性的方式结合CRL2组件。 lrr-1功能的丧失会导致细胞周期停滞在生殖细胞的有丝分裂区域，由于生殖细胞的消耗而导致不育。 DNA复制检查点信号组件ATL-1和CHK-1的失活抑制了该细胞周期停滞，并显着恢复了lrr-1突变体的生育能力。同样，在早期胚胎中，lrr-1功能的丧失会诱导CHK-1磷酸化并在P谱系分裂中造成严重的细胞周期延迟，从而导致胚胎致死率。检查点激活在lrr-1突变体中不是组成性的，而是由DNA损伤诱导的，DNA损伤可能是由于基因组某些区域的复制而引起的，单链DNA复制蛋白A（ssDNA-RPA- 1）核灶和lrr-1和lrr-1中生殖细胞倍性的增加; atl-1双重突变体。总的来说，这些观察通过在秀丽隐杆线虫发育过程中维持DNA复制完整性突出了CRL2（LRR-1）复合物在基因组稳定性中的关键功能。

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