Sae2 and Rif2 regulate MRX endonuclease activity at DNA double-strand breaks in opposite manners

• DOI: 10.1016/j.celrep.2021.108906
• Publication Date: 2021-03-31T00:55:27Z
• Authors: Antonio Marsella; Elisa Gobbini; Corinne Cassani; Renata Tisi; Elda Cannavo; Giordano Reginato; Petr Cejka; Maria Pia Longhese
• Keywords: Nuclease; Rad50; Cleavage (geology)

The Mre11-Rad50-Xrs2 (MRX) complex detects and processes DNA double-strand breaks (DSBs). Its binding processing activities are regulated by transitions between an ATP-bound state a post-hydrolysis cutting that is nucleolytically active. Mre11 endonuclease activity stimulated Sae2, whose lack increases MRX persistence at DSBs checkpoint activation. Here we show the Rif2 protein inhibits responsible for increased retention in sae2Δ cells. We identify Rad50 residue important Rad50-Rif2 interaction inhibition of nuclease. This located near surface binds Sae2 stabilizing Mre11-Rad50 (MR) state. propose stimulates MR conformation competent cleavage, whereas antagonizes this function stabilizes inactive conformation.