MRNIP Condensates Promote DNA Double-strand Break Sensing and End Resection

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 13

PMID 35551189

Authors

Yun-Long Wang

Wan-Wen Zhao

Shao-Mei Bai

Li-Li Feng

Shu-Ying Bie

Li Gong

Fang Wang

Ming-Biao Wei

Wei-Xing Feng

Xiao-Lin Pang

Cao-Litao Qin

Xin-Ke Yin

Ying-Nai Wang

Weihua Zhou

Daniel R Wahl

Quentin Liu

Ming Chen

Mien-Chie Hung

Xiang-Bo Wan

Affiliations

Soon will be listed here.

Abstract

The rapid recognition of DNA double-strand breaks (DSBs) by the MRE11/RAD50/NBS1 (MRN) complex is critical for the initiation of DNA damage response and DSB end resection. Here, we show that MRN complex interacting protein (MRNIP) forms liquid-like condensates to promote homologous recombination-mediated DSB repair. The intrinsically disordered region is essential for MRNIP condensate formation. Mechanically, the MRN complex is compartmentalized and concentrated into MRNIP condensates in the nucleus. After DSB formation, MRNIP condensates move to the damaged DNA rapidly to accelerate the binding of DSB by the concentrated MRN complex, therefore inducing the autophosphorylation of ATM and subsequent activation of DNA damage response signaling. Meanwhile, MRNIP condensates-enhanced MRN complex loading further promotes DSB end resection. In addition, data from xenograft models and clinical samples confirm a correlation between MRNIP and radioresistance. Together, these results reveal an important role of MRNIP phase separation in DSB response and the MRN complex-mediated DSB end resection.

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