The DNA Damage Repair Function of Fission Yeast CK1 Involves Targeting Arp8, a Subunit of the INO80 Chromatin Remodeling Complex

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2024 Oct 10

PMID 39387272

Authors

Sierra N Cullati

Kazutoshi Akizuki

Yufan Shan

Eric Zhang

Liping Ren

Rodrigo X Guillen

Lesley A Turner

Jun-Song Chen

Jose Navarrete-Perea

Zachary C Elmore

Steven P Gygi

Kathleen L Gould

Affiliations

Soon will be listed here.

Abstract

The CK1 family are conserved serine/threonine kinases with numerous substrates and cellular functions. The fission yeast CK1 orthologues Hhp1 and Hhp2 were first characterized as regulators of DNA repair, but the mechanism(s) by which CK1 activity promotes DNA repair had not been investigated. Here, we found that deleting Hhp1 and Hhp2 or inhibiting CK1 catalytic activities in yeast or in human cells increased double-strand breaks (DSBs). The primary pathways to repair DSBs, homologous recombination and nonhomologous end joining, were both less efficient in cells lacking Hhp1 and Hhp2 activity. To understand how Hhp1 and Hhp2 promote DNA damage repair, we identified new substrates of these enzymes using quantitative phosphoproteomics. We confirmed that Arp8, a component of the INO80 chromatin remodeling complex, is a bona fide substrate of Hhp1 and Hhp2 important for DNA repair. Our data suggest that Hhp1 and Hhp2 facilitate DNA repair by phosphorylating multiple substrates, including Arp8.

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