Uckelmann Michael, Sixma Titia K
Division of Biochemistry and Cancer Genomics Centre, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Division of Biochemistry and Cancer Genomics Centre, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
DNA Repair (Amst). 2017 Aug;56:92-101. doi: 10.1016/j.dnarep.2017.06.011. Epub 2017 Jun 9.
DNA double strand breaks need to be repaired in an organized fashion to preserve genomic integrity. In the organization of faithful repair, histone ubiquitination plays a crucial role. Recent findings suggest an integrated model for DNA repair regulation through site-specific histone ubiquitination and crosstalk to other posttranslational modifications. Here we discuss how site-specific histone ubiquitination is achieved on a molecular level and how different multi-protein complexes work together to integrate different histone ubiquitination states. We propose a model where site-specific H2A ubiquitination organizes the spatio-temporal recruitment of DNA repair factors which will ultimately contribute to DNA repair pathway choice between homologous recombination and non-homologous end joining.
DNA双链断裂需要以有组织的方式进行修复，以维持基因组的完整性。在精确修复的组织过程中，组蛋白泛素化起着关键作用。最近的研究结果提出了一个通过位点特异性组蛋白泛素化以及与其他翻译后修饰的相互作用来调控DNA修复的整合模型。在这里，我们讨论了在分子水平上如何实现位点特异性组蛋白泛素化，以及不同的多蛋白复合物如何协同工作以整合不同的组蛋白泛素化状态。我们提出了一个模型，其中位点特异性H2A泛素化组织DNA修复因子的时空募集，这最终将有助于在同源重组和非同源末端连接之间选择DNA修复途径。
