Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
J Cell Biol. 2010 Oct 18;191(2):249-57. doi: 10.1083/jcb.201005101. Epub 2010 Oct 11.
The Fanconi anemia (FA) network is important for the repair of interstrand DNA cross-links. A key event in FA pathway activation is the monoubiquitylation of the FA complementation group I (FANCI)-FANCD2 (ID) complex by FA complementation group L (FANCL), an E3 ubiquitin ligase. In this study, we show that RAD18, another DNA damage-activated E3 ubiquitin ligase, also participates in ID complex activation by ubiquitylating proliferating cell nuclear antigen (PCNA) on Lys164, an event required for the recruitment of FANCL to chromatin. We also found that monoubiquitylated PCNA stimulates FANCL-catalyzed FANCD2 and FANCI monoubiquitylation. Collectively, these experiments identify RAD18-mediated PCNA monoubiquitination as a central hub for the mobilization of the FA pathway by promoting FANCL-mediated FANCD2 monoubiquitylation.
范可尼贫血（FA）网络对于修复链间 DNA 交联至关重要。FA 途径激活的一个关键事件是 FA 补体组 I（FANCI）-FANCD2（ID）复合物被 E3 泛素连接酶 FA 补体组 L（FANCL）单泛素化。在这项研究中，我们表明另一种 DNA 损伤激活的 E3 泛素连接酶 RAD18 也通过在赖氨酸 164 上泛素化增殖细胞核抗原（PCNA）参与 ID 复合物的激活，该事件需要 FANCL 募集到染色质。我们还发现单泛素化的 PCNA 刺激 FANCL 催化的 FANCD2 和 FANCI 单泛素化。总之，这些实验确定 RAD18 介导的 PCNA 单泛素化作为通过促进 FANCL 介导的 FANCD2 单泛素化来动员 FA 途径的中心枢纽。
