XLF/Cernunnos：非同源末端连接DNA修复途径中一个重要但令人费解的参与者。
XLF/Cernunnos: An important but puzzling participant in the nonhomologous end joining DNA repair pathway.
作者信息
Menon Vijay, Povirk Lawrence F
机构信息
Goodwin Research Laboratory, Massey Cancer Center, Virginia Commonwealth University, VA, USA.
Goodwin Research Laboratory, Massey Cancer Center, Virginia Commonwealth University, VA, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University, VA, USA.
出版信息
DNA Repair (Amst). 2017 Oct;58:29-37. doi: 10.1016/j.dnarep.2017.08.003. Epub 2017 Aug 18.
DNA double strand breaks (DSBs) are one of the most deleterious DNA lesions that promote cell death, genomic instability and carcinogenesis. The two major cellular mechanisms that repair DSBs are Nonhomologous End-Joining (NHEJ) and Homologous Recombination Repair (HRR). NHEJ is the predominant pathway, in which XLF (also called Cernunnos) is a key player. Patients with XLF mutation exhibit microcephaly, lymphopenia, and growth retardation, and are immunodeficient and radiosensitive. During NHEJ, XLF interacts with XRCC4-Ligase IV, stimulates its ligase activity, and forms DNA-binding filaments of alternating XLF and XRCC4 dimers that may serve to align broken DNA and promote ligation of noncomplementary ends. Despite its central role in NHEJ, the effects of XLF deficiency are surprisingly variable in different biological contexts, and different individual cell lines. This review summarizes the role of XLF in NHEJ, and the unexpected complexity of its interplay with other repair factors in supporting radiosurvival and V(D)J recombination.
DNA双链断裂（DSB）是最具危害性的DNA损伤之一，可促进细胞死亡、基因组不稳定和致癌作用。修复DSB的两种主要细胞机制是非同源末端连接（NHEJ）和同源重组修复（HRR）。NHEJ是主要途径，其中XLF（也称为Cernunnos）是关键因素。XLF突变患者表现出小头畸形、淋巴细胞减少和生长发育迟缓，并且免疫缺陷和对辐射敏感。在NHEJ过程中，XLF与XRCC4-连接酶IV相互作用，刺激其连接酶活性，并形成由交替的XLF和XRCC4二聚体组成的DNA结合细丝，这些细丝可能用于对齐断裂的DNA并促进非互补末端的连接。尽管XLF在NHEJ中起核心作用，但在不同的生物学背景和不同的个体细胞系中，XLF缺乏的影响出人意料地多变。本综述总结了XLF在NHEJ中的作用，以及其与其他修复因子在支持辐射存活和V（D）J重组中的相互作用所具有的意外复杂性。
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