增殖细胞核抗原
泛素
泛素结合酶
相扑酶
DNA修复
生物
DNA损伤
染色质
DNA
生物化学
DNA聚合酶
细胞生物学
DNA钳
赖氨酸
分子生物学
相扑蛋白
泛素连接酶
逆转录酶
基因
核糖核酸
氨基酸
作者
Carsten Hoege,Boris Pfander,George‐Lucian Moldovan,George Pyrowolakis,Stefan Jentsch
出处
期刊:Nature
[Springer Nature]
日期:2002-09-01
卷期号:419 (6903): 135-141
被引量:1990
摘要
The RAD6 pathway is central to post-replicative DNA repair in eukaryotic cells; however, the machinery and its regulation remain poorly understood. Two principal elements of this pathway are the ubiquitin-conjugating enzymes RAD6 and the MMS2-UBC13 heterodimer, which are recruited to chromatin by the RING-finger proteins RAD18 and RAD5, respectively. Here we show that UBC9, a small ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that proliferating cell nuclear antigen (PCNA) -- a DNA-polymerase sliding clamp involved in DNA synthesis and repair -- is a substrate. PCNA is mono-ubiquitinated through RAD6 and RAD18, modified by lysine-63-linked multi-ubiquitination--which additionally requires MMS2, UBC13 and RAD5--and is conjugated to SUMO by UBC9. All three modifications affect the same lysine residue of PCNA, suggesting that they label PCNA for alternative functions. We demonstrate that these modifications differentially affect resistance to DNA damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans.
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