Spartan deficiency causes genomic instability and progeroid phenotypes.
Spartan deficiency causes genomic instability and progeroid phenotypes.
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DOI：
10.1038/ncomms6744
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发表时间：
2014-12-11
影响因子：
16.6
通讯作者：
Machida, Yuichi J.
中科院分区：
文献类型：
--
作者：
Maskey, Reeja S.;Kim, Myoung Shin;Baker, Darren J.;Childs, Bennett;Malureanu, Liviu A.;Jeganathan, Karthik B.;Machida, Yuka;van Deursen, Jan M.;Machida, Yuichi J.
Spartan（也称为DVC1和C1orf124）是一种与翻译合成有关的pca相互作用蛋白，翻译合成是一种DNA损伤耐受过程，允许DNA复制机制复制过去的核苷酸损伤。然而，斯巴达的生理相关性尚未确定。在这里，我们报告斯巴达不足在小鼠中导致染色体不稳定，细胞衰老和年龄相关表型的早期发作。然而完全丧失斯巴达基因会导致早期胚胎死亡，低斯巴达基因的半胚小鼠是可以存活的。这些小鼠生长迟缓，在幼年时发展为白内障、脊柱前突和恶病质。从条件敲除小鼠胚胎成纤维细胞中，cre介导的斯巴达消耗导致病变旁路受损，DNA复制不完全，微核和染色质桥的形成，最终导致细胞死亡。这些数据表明，Spartan在维持染色体结构和数量完整性方面起着关键作用，并提示Spartan不足与早衰症之间存在联系。Spartan/DVC1是一种翻译合成调节剂，在细胞DNA损伤耐受中起重要作用。在这里，作者报告说，斯巴达是DNA病变绕道所必需的，斯巴达不足会导致小鼠染色体不稳定、细胞衰老和年龄相关表型的早期发作。
Spartan (also known as DVC1 and C1orf124) is a PCNA-interacting protein implicated in translesion synthesis, a DNA damage tolerance process that allows the DNA replication machinery to replicate past nucleotide lesions. However, the physiological relevance of Spartan has not been established. Here we report that Spartan insufficiency in mice causes chromosomal instability, cellular senescence and early onset of age-related phenotypes. Whereas complete loss of Spartan causes early embryonic lethality, hypomorphic mice with low amounts of Spartan are viable. These mice are growth retarded and develop cataracts, lordokyphosis and cachexia at a young age. Cre-mediated depletion of Spartan from conditional knockout mouse embryonic fibroblasts results in impaired lesion bypass, incomplete DNA replication, formation of micronuclei and chromatin bridges and eventually cell death. These data demonstrate that Spartan plays a key role in maintaining structural and numerical chromosome integrity and suggest a link between Spartan insufficiency and progeria. Spartan/DVC1 is a translesion synthesis regulator with important roles in cellular DNA damage tolerance. Here, the authors report that Spartan is essential for DNA lesion bypass and that Spartan insufficiency in mice causes chromosomal instability, cellular senescence and early onset of age-related phenotypes.
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影响因子：
4.5
作者：
Hendel A;Krijger PH;Diamant N;Goren Z;Langerak P;Kim J;Reissner T;Lee KY;Geacintov NE;Carell T;Myung K;Tateishi S;D'Andrea A;Jacobs H;Livneh Z
通讯作者：
Livneh Z
影响因子：
14.9
作者：
Kim MS;Machida Y;Vashisht AA;Wohlschlegel JA;Pang YP;Machida YJ
通讯作者：
Machida YJ
影响因子：
4.8
作者：
Dawlaty, Meelad M.;van Deursen, Jan M.
通讯作者：
van Deursen, Jan M.
影响因子：
2.8
作者：
Barclay, WW;Cramer, SD
通讯作者：
Cramer, SD
影响因子：
16
作者：
Centore, Richard C.;Yazinski, Stephanie A.;Tse, Alice;Zou, Lee
通讯作者：
Zou, Lee