Phosphorylation of Sae2 Mediates Forkhead-associated (FHA) Domain-specific Interaction and Regulates Its DNA Repair Function.

The Journal of Biological Chemistry
Jason LiangHuilin Zhou

Abstract

Saccharomyces cerevisiae Sae2 and its ortholog CtIP in higher eukaryotes have a conserved role in the initial processing of DNA lesions and influencing their subsequent repair pathways. Sae2 is phosphorylated by the ATR/ATM family kinases Mec1 and Tel1 in response to DNA damage. Among the Mec1/Tel1 consensus phosphorylation sites of Sae2, we found that mutations of Thr-90 and Thr-279 of Sae2 into alanine caused a persistent Rad53 activation in response to a transient DNA damage, similar to the loss of Sae2. To gain insight into the function of this phosphorylation of Sae2, we performed a quantitative proteomics analysis to identify its associated proteins. We found that phosphorylation of Thr-90 of Sae2 mediates its interaction with Rad53, Dun1, Xrs2, Dma1, and Dma2, whereas Rad53 and Dun1 additionally interact with phosphorylated Thr-279 of Sae2. Mutations of the ligand-binding residues of Forkhead-associated (FHA) domains of Rad53, Dun1, Xrs2, Dma1, and Dma2 abolished their interactions with Sae2, revealing the involvement of FHA-specific interactions. Mutations of Thr-90 and Thr-279 of Sae2 caused a synergistic defect when combined with sgs1Δ and exo1Δ and elevated gross chromosomal rearrangements. Likewise, mutations of RAD...Continue Reading

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Citations

Apr 22, 2016·Critical Reviews in Biochemistry and Molecular Biology·Lorraine S Symington
Oct 22, 2016·Molecular Cell·Julyun OhLorraine S Symington
Aug 9, 2019·The EMBO Journal·Michael Charles LanzMarcus Bustamante Smolka
Dec 13, 2018·Genetics·Chiara Vittoria ColomboMaria Pia Longhese
Dec 5, 2018·Proceedings of the National Academy of Sciences of the United States of America·Tai-Yuan YuLorraine S Symington
Sep 26, 2019·Nucleic Acids Research·Tai-Yuan YuLorraine S Symington
Dec 7, 2018·Genes·Julyun Oh, Lorraine S Symington
Sep 16, 2019·International Journal of Biological Macromolecules·Nikhilesh Joardar, Santi P Sinha Babu
Jun 2, 2020·DNA Repair·Giordano Reginato, Petr Cejka
Mar 23, 2021·Frontiers in Cell and Developmental Biology·Vikash Kumar Yadav, Corentin Claeys Bouuaert
May 3, 2021·The Journal of Biological Chemistry·Andrew R YoblinskiRaghuvar Dronamraju

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