浙江大學生命科學研究院劉婷博士和黃俊博士2010年10月22日在DNA Repair雜志在線發(fā)表綜述文章“RAD18 lives a double life: its implication in DNA double-strand break repair”,。其中劉婷博士為第一作者,，黃俊博士與M.D.Anderson Cancer Center的Dr.Junjie Chen為共同通訊作者,。
泛素E3連接酶RAD18在真核生物中十分保守,，長期以來,，RAD18在DNA損傷的復制后修復中的重要作用備受研究者關(guān)注,。如果受到損傷的DNA在真核細胞進入DNA合成的S 期之前還未得到修復,，細胞將會啟動DNA損傷耐受機制（DDT,DNA damage tolerance）以順利完成DNA復制,。PCNA泛素化是DTT過程中的關(guān)鍵步驟,，被單泛素化后的PCNA進而招募一系列非特異性DNA合成酶到DNA損傷位點，從而完成在DNA損傷存在條件下的DNA合成,。而研究者們發(fā)現(xiàn),，對PCNA的泛素化主要是通過RAD18-RAD6這一E3-E2復合物完成。
除了復制后修復,，很多研究表明RAD18可能在同源重組修復過程中也行使重要作用。在DNA雙鏈損傷后,，RNF8/UBC13泛素化H2A/H2AX,，RAD18通過與H2A/H2AX的泛素化鏈相結(jié)合被招募到損傷位點，進而通過招募RAD51C參與DNA修復,。這一過程不止在DNA同源重組修復中起重要作用，還作為DNA修復以及DNA檢驗點啟動之間的平衡調(diào)節(jié)過程而在DNA損傷修復中行使重要功能,。
本綜述詳盡闡述了RAD18蛋白在DNA損傷的復制后修復以及同源重組修復中的重要功能和作用機制。(生物谷Bioon.com)
生物谷推薦英文摘要：
DNA Repair PMID: 20971043
RAD18 livesadoublelife:ItsimplicationinDNAdouble-strandbreakrepair
Ting L, Jun H, Junjie C.
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Maintenance of genome stability depends on efficient and accurate repair of DNA lesions. Failure to properly repair damaged DNA can cause cell death, mutations and chromosomal instability, which eventually lead to tumorigenesis. The E3 ligase RAD18 is well-known for its function in DNA damage bypass and post-replication repair (PRR) in yeast and vertebrates via its ability to facilitate PCNA mono-ubiquitination at stalled replication forks. However, emerging evidence has also indicated that RAD18 plays an important role in homologous recombination (HR) in mammalian cells, which is an error-free DNA repair pathway that mediates the repair of double-strand breaks (DSBs). Here, we review how RAD18 carries out these distinct functions in response to different types of DNA lesions.
