DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation
DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation
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DOI：
10.1128/mcb.24.24.10733-10741.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
Takata, M
中科院分区：
文献类型：
--
作者：
Ishiai, M;Kimura, M;Takata, M
酵母SNM 1/PSO 2基因在DNA链间交联（ICL）修复中特异性发挥作用，并且其作用已被认为与其他DNA修复途径不同。在脊椎动物中，有三种SNM 1的同源物（SNM 1A，SNM 1B和SNM 1C/Artemis; SNM 1家族蛋白），其功能在很大程度上是未知的。我们破坏了鸡B细胞系DT 40中SNN 1家族的每一个基因。SNM 1A和SNM 1B缺陷细胞对顺铂敏感，但对X射线不敏感，而SNM 1C/Artemis缺陷细胞对X射线敏感，但对顺铂不敏感。SNM 1A与XRCC 3（同源重组），RAD 18（跨损伤合成），FANCC（范可尼贫血）和SNM 1B在ICL修复中是非上位性的。SNM 1A蛋白依赖于保守的SNM 1（金属β-内酰胺酶）结构域形成点状核灶。PIAS 1被发现与SNM 1A物理相互作用，并且它们共定位于核灶。SNM 1结构域中的点突变破坏了与PIAS 1的相互作用，导致SNM 1A在细胞核中的错误定位和snm 1a细胞互补的丧失。这些结果表明，SNM 1A和PIAS 1之间的相互作用是ICL修复所必需的。
The yeast SNM1/PSO2 gene specifically functions in DNA interstrand cross-link (ICL) repair, and its role has been suggested to be separate from other DNA repair pathways. In vertebrates, there are three homologs of SNM1 (SNM1A, SNM1B, and SNM1C/Artemis; SNM1 family proteins) whose functions are largely unknown. We disrupted each of the SNN1 family genes in the chicken B-cell line DT40. Both SNM1A- and SNM1B-deficient cells were sensitive to cisplatin but not to X-rays, whereas SNM1C/Artemis-deficient cells exhibited sensitivity to X-rays but not to cisplatin. SNM1A was nonepistatic with XRCC3 (homologous recombination), RAD18 (translesion synthesis), FANCC (Fanconi anemia), and SNM1B in ICL repair. SNM1A protein formed punctate nuclear foci depending on the conserved SNM1 (metallo-beta-lactamase) domain. PIAS1 was found to physically interact with SNM1A, and they colocalized at nuclear foci. Point mutations in the SNM1 domain, which disrupted the interaction with PIAS1, led to mislocalization of SNM1A in the nucleus and loss of complementation of snm1a cells. These results suggest that interaction between SNM1A and PIAS1 is required for ICL repair.