复制独立的 DNA 链间交联修复。
Replication-independent repair of DNA interstrand crosslinks.
机构信息
Institute for Cancer Genetics, Department of Genetics and Development, Columbia University, New York, NY 10032, USA.
出版信息
Mol Cell. 2012 Jul 13;47(1):140-7. doi: 10.1016/j.molcel.2012.05.001. Epub 2012 May 31.
Abstract
DNA interstrand crosslinks (ICLs) are cytotoxic lesions that covalently link opposite strands of the DNA helix and block DNA unwinding. ICLs are repaired during and outside S phase, and replication-independent ICL repair (RIR) is critical to maintain genomic integrity and to allow transcription in nondividing or slowly dividing cells. Here, we show that the Y family DNA polymerase kappa (Pol κ) is essential for RIR of a site-specific ICL lesion in Xenopus egg extracts, and that both its catalytic activity and UBZ domains are required for this function. We also demonstrate a requirement for PCNA and its modification on lysine 164. Finally, we show that Pol κ participates in ICL repair in mammalian cells, particularly in G0. Our results identify key components of the RIR pathway and begin to unravel its mechanism.
摘要
DNA 链间交联 (ICLs) 是一种细胞毒性损伤，它使 DNA 双螺旋的两条互补链共价连接，并阻止 DNA 解旋。ICLs 在 S 期内外被修复，而不依赖于复制的 ICL 修复 (RIR) 对于维持基因组完整性和允许转录在非分裂或缓慢分裂的细胞中至关重要。在这里，我们表明 Y 家族 DNA 聚合酶 κ (Pol κ) 对于爪蟾卵提取物中特定位置的 ICL 损伤的 RIR 是必需的，并且其催化活性和 UBZ 结构域对于该功能都是必需的。我们还证明了 PCNA 及其赖氨酸 164 上的修饰的必要性。最后，我们表明 Pol κ 参与了哺乳动物细胞中的 ICL 修复，特别是在 G0 期。我们的结果确定了 RIR 途径的关键组成部分，并开始揭示其机制。
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