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首页> 外文期刊>Cell cycle >Human KIAA1018/FAN1 localizes to stalled replication forks via its ubiquitin-binding domain.
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Human KIAA1018/FAN1 localizes to stalled replication forks via its ubiquitin-binding domain.

机译：人类KIAA1018 / FAN1通过其泛素结合域定位到停滞的复制叉。

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摘要

Genome maintenance pathways correct aberrations in DNA that would be deleterious to the organism. A crucial element of many genome maintenance processes is the ability to degrade DNA that either contains errors or obscures useful substrates for recombination and/or repair by means of nucleases. We have examined a putative nuclease that has heretofore been unreported, KIAA1018/FAN1. This protein contains a predicted ubiquitin-binding zinc finger domain (UBZ) near its N-terminus and an endonuclease-like fold near its C-terminus. Here we describe that FAN1 is a nuclear protein and forms DNA-damage-induced foci, which appear to be at stalled replication forks as denoted by RPA colocalization. Localization of FAN1 to sites of damage is dependent upon its UBZ domain. In addition, knockdown of FAN1 by RNA interference leads to increased sensitivity to interstrand crosslinking agents and accumulation of abnormal chromosomes. FAN1 may be an important new player in the maintenance of genome stability.
机译：基因组维持途径纠正了对生物体有害的DNA畸变。许多基因组维持过程的关键要素是能够降解包含错误或掩盖有用底物的DNA的能力，以便通过核酸酶进行重组和/或修复。我们已经检查了迄今尚未报道的推定核酸酶KIAA1018 / FAN1。该蛋白质在其N末端附近包含一个预测的泛素结合锌指结构域（UBZ），在其C末端附近包含一个核酸内切酶样折叠。在这里，我们描述FAN1是一种核蛋白，并形成DNA损伤诱导的病灶，这似乎是停滞的复制叉，如RPA共定位所表示。 FAN1在损伤部位的定位取决于其UBZ域。另外，通过RNA干扰敲低FAN1导致对链间交联剂的敏感性增加，并导致异常染色体的积累。 FAN1可能是维持基因组稳定性的重要新角色。

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