Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Cell Biol. 2009 Nov 2;187(3):319-26. doi: 10.1083/jcb.200908074.
The intimate relationship between DNA double-strand break (DSB) repair and cancer susceptibility has sparked profound interest in how transactions on DNA and chromatin surrounding DNA damage influence genome integrity. Recent evidence implicates a substantial commitment of the cellular DNA damage response machinery to the synthesis, recognition, and hydrolysis of ubiquitin chains at DNA damage sites. In this review, we propose that, in order to accommodate parallel processes involved in DSB repair and checkpoint signaling, DSB-associated ubiquitin structures must be nonuniform, using different linkages for distinct functional outputs. We highlight recent advances in the study of nondegradative ubiquitin signaling at DSBs, and discuss how recognition of different ubiquitin structures may influence DNA damage responses.
DNA 双链断裂 (DSB) 修复与癌症易感性之间的密切关系，激发了人们对 DNA 和染色质周围与 DNA 损伤相关的交易如何影响基因组完整性的极大兴趣。最近的证据表明，细胞 DNA 损伤反应机制大量投入到 DNA 损伤部位的泛素链的合成、识别和水解中。在这篇综述中，我们提出，为了适应 DSB 修复和检查点信号转导中涉及的平行过程，DSB 相关的泛素结构必须是非均匀的，使用不同的连接来产生不同的功能输出。我们强调了在 DSB 上非降解泛素信号研究方面的最新进展，并讨论了识别不同的泛素结构如何影响 DNA 损伤反应。
