The 14-3-3 gene par-5 is required for germline development and DNA damage response in Caenorhabditis elegans
The 14-3-3 gene par-5 is required for germline development and DNA damage response in Caenorhabditis elegans
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DOI：
10.1242/jcs.094896
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发表时间：
2012-04-01
影响因子：
4
通讯作者：
Schwartz, Simo, Jr.
中科院分区：
文献类型：
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作者：
Aristizabal-Corrales, David;Fontrodona, Laura;Schwartz, Simo, Jr.
14-3-3蛋白在从酵母到哺乳动物的各种生物中都得到了广泛的研究，并与多种功能有关，包括细胞周期、细胞凋亡和应激反应等基本过程，以及对癌症等疾病的反应。在秀丽线虫中，有两个14-3-3基因，即FTT-2和PAR-5。FTT-2只在体细胞系中表达，而PAR-5在胞体和生殖系中都有表达。在早期胚胎发育中，PAR-5是建立细胞极性所必需的。虽然已知PAR-5失活会导致不育，但该基因在生殖系发育中的作用尚不清楚。在本研究中，我们使用PAR-5突变和RNA干扰来表征胚系中PAR-5的功能。生殖细胞中PAR-5的缺失导致细胞周期紊乱、内源性DNA损伤积累和基因组不稳定。此外，PAR-5是检查点诱导的细胞周期停滞所必需的，以响应DNA损伤剂。我们提出了一个模型，在该模型中，PAR-5调节CDK-1的磷酸化，以防止过早进入有丝分裂。这项研究为研究14-3-3功能的机制开辟了一条新的途径，14-3-3功能不仅对线虫的发育至关重要，而且在人类疾病中也被证明是改变的。
14-3-3 proteins have been extensively studied in organisms ranging from yeast to mammals and are associated with multiple roles, including fundamental processes such as the cell cycle, apoptosis and the stress response, to diseases such as cancer. In Caenorhabditis elegans, there are two 14-3-3 genes, ftt-2 and par-5. ftt-2 is expressed only in somatic lineages, whereas par-5 expression is detected in both soma and germline. During early embryonic development, par-5 is necessary to establish cell polarity. Although it is known that par-5 inactivation results in sterility, the role of this gene in germline development is poorly characterized. In the present study, we used a par-5 mutation and RNA interference to characterize par-5 functions in the germline. The lack of par-5 in germ cells caused cell cycle deregulation, the accumulation of endogenous DNA damage and genomic instability. Moreover, par-5 was required for checkpoint-induced cell cycle arrest in response to DNA-damaging agents. We propose a model in which PAR-5 regulates CDK-1 phosphorylation to prevent premature mitotic entry. This study opens a new path to investigate the mechanisms of 14-3-3 functions, which are not only essential for C. elegans development, but have also been shown to be altered in human diseases.