Essential Role of Ubiquitin-Fold Modifier 1 Conjugation in DNA Damage Response
Essential Role of Ubiquitin-Fold Modifier 1 Conjugation in DNA Damage Response
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泛素折叠修饰符 1 缀合在 DNA 损伤反应中的重要作用
DOI：
10.1089/dna.2019.4861
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发表时间：
2019-08-01
影响因子：
3.1
通讯作者：
Pan, Zezheng
中科院分区：
文献类型：
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作者：
Fang, Zhi;Pan, Zezheng
内源性和外源性因素都可能导致DNA损伤，损害基因组完整性和细胞活力。适当的DNA损伤反应（DDR）在维持基因组稳定性和防止肿瘤发生中起着重要作用。DNA双链断裂（DSBs）是最具毒性的DNA损伤，其反应主要是共济失调-毛细血管扩张突变（ATM）蛋白激酶。在被传感器Mre11-Rad50-Nbs1 （MRN）复合物或乙酰转移酶Tip60激活后，当DNA受损时，ATM迅速磷酸化下游靶标以启动DDR信号。然而，DDR的确切机制是复杂和模糊的。泛素化修饰是一类泛素样修饰，主要通过三步酶促反应帮助泛素折叠修饰物1 （Ufm1）通过泛素样修饰物激活酶5 （Uba5）、泛素样修饰物偶联酶1 （Ufc1）和泛素样修饰物特异性连接酶1 （Ufl1）附着在底物上。尽管泛素化对DSBs应答至关重要，但泛素化在DDR中的潜在功能在很大程度上是未知的。本文就ufmyation与DDR之间的关系进行综述，旨在阐明ufmyation在DDR中的作用和机制，为揭示一些疾病的发病机制和创造新的治疗方法提供新的指导。
Both endogenous and exogenous factors can cause DNA damage that compromises genomic integrity and cell viability. A proper DNA damage response (DDR) plays a role in maintaining genome stability and preventing tumorigenesis. DNA double-strand breaks (DSBs) are the most toxic DNA lesion, whose response is dominated by the ataxia-telangiectasia mutated (ATM) protein kinase. After being activated by the sensor Mre11-Rad50-Nbs1 (MRN) complex or acetyltransferase Tip60, ATM rapidly phosphorylates downstream targets to launch DDR signaling when DNA is damaged. However, the exact mechanism of DDR is complex and ambiguous. Ufmylation, one type of ubiquitin-like modification, proceeds mainly through a three-step enzymatic reaction to help ubiquitin-fold modifier 1 (Ufm1), attach to substrates with ubiquitin-like modifier-activating enzyme 5 (Uba5), Ufm1-conjugating enzyme 1 (Ufc1) and Ufm1-specific ligase 1 (Ufl1). Although ubiquitination is essential to the DSBs response, the potential function of ufmylation in DDR is largely unknown. Herein, we review the relationship between ufmylation and DDR to elucidate the function and mechanism of ufmylation in DDR, which would reveal the pathogenesis of some diseases and provide new guidance to create a therapeutic method.