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Reference - PMID:39387272 - The DNA Damage Repair Function of Fission Yeast CK1 Involves Targeting Arp8, a Subunit of the INO80 Chromatin Remodeling Complex.

Reference summary

PubMed ID
PMID:39387272
Title
The DNA Damage Repair Function of Fission Yeast CK1 Involves Targeting Arp8, a Subunit of the INO80 Chromatin Remodeling Complex.
Authors
Cullati SN, Akizuki K, Shan Y, Zhang E, Ren L, Guillen RX, Turner LA, Chen JS, Navarrete-Perea J, Elmore ZC, Gygi SP, Gould KL
Citation
Mol Cell Biol 2024 Oct 10;:1-15
Publication year
2024
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.

Annotation

GO biological process

GO:2000781 - positive regulation of double-strand break repair

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GO cellular component

GO:0035861 - site of double-strand break

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Modification

MOD:00046 - O-phospho-L-serine

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Multi-locus phenotype

FYPO:0000082 - decreased cell population growth at high temperature

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Genotypes:

FYPO:0003660 - decreased double-strand break repair during vegetative growth

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FYPO:0003912 - decreased double-strand break repair via homologous recombination

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FYPO:0004287 - decreased double-strand break repair via nonhomologous end joining

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FYPO:0001355 - decreased vegetative cell population growth

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FYPO:0001122 - elongated vegetative cell

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FYPO:0004709 - increased number of Rad52 foci

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FYPO:0000674 - normal cell population growth at high temperature

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FYPO:0001357 - normal vegetative cell population growth

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FYPO:0000085 - sensitive to camptothecin

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FYPO:0000088 - sensitive to hydroxyurea

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FYPO:0000089 - sensitive to methyl methanesulfonate

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Single locus phenotype

FYPO:0000082 - decreased cell population growth at high temperature

Genes:

Genotypes:

FYPO:0003912 - decreased double-strand break repair via homologous recombination

Genes:

Genotypes:

FYPO:0004287 - decreased double-strand break repair via nonhomologous end joining

Genes:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

Genes:

Genotypes:

FYPO:0001122 - elongated vegetative cell

Genes:

Genotypes:

FYPO:0004709 - increased number of Rad52 foci

Genes:

Genotypes:

FYPO:0000674 - normal cell population growth at high temperature

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Genotypes:

FYPO:0001690 - normal growth on camptothecin

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Genotypes:

FYPO:0000957 - normal growth on methyl methanesulfonate

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Genotypes:

FYPO:0001357 - normal vegetative cell population growth

Genes:

Genotypes:

FYPO:0000085 - sensitive to camptothecin

Genes:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

Genes:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

Genes:

Genotypes: