Details

Autor(en) / Beteiligte

• Gao, Ming
• Guo, Guijie
• Huang, Jinzhou
• Kloeber, Jake A.
• Zhao, Fei
• Deng, Min
• Tu, Xinyi
• Kim, Wootae
• Zhou, Qin
• Zhang, Chao
• Yin, Ping
• Luo, Kuntian
• Lou, Zhenkun

Titel

USP52 regulates DNA end resection and chemosensitivity through removing inhibitory ubiquitination from CtIP

Ist Teil von

• Nature communications, 2020-10, Vol.11 (1), p.1-13, Article 5362

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Human C-terminal binding protein (CtBP)–interacting protein (CtIP) is a central regulator to initiate DNA end resection and homologous recombination (HR). Several studies have shown that post-translational modifications control the activity or expression of CtIP. However, it remains unclear whether and how cells restrain CtIP activity in unstressed cells and activate CtIP when needed. Here, we identify that USP52 directly interacts with and deubiquitinates CtIP, thereby promoting DNA end resection and HR. Mechanistically, USP52 removes the ubiquitination of CtIP to facilitate the phosphorylation and activation of CtIP at Thr-847. In addition, USP52 is phosphorylated by ATM at Ser-1003 after DNA damage, which enhances the catalytic activity of USP52. Furthermore, depletion of USP52 sensitizes cells to PARP inhibition in a CtIP-dependent manner in vitro and in vivo. Collectively, our findings reveal the key role of USP52 and the regulatory complexity of CtIP deubiquitination in DNA repair.