Regulation of Elg1 activity by phosphorylation

Dganit Shkedy, Nishant Singh, Keren Shemesh, Ayelet Amir, Tamar Geiger, Batia Liefshitz, Yaniv Harari, Martin Kupiec*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

ELG1 is a conserved gene with important roles in the maintenance of genome stability. Elg1‘s activity prevents gross chromosomal rearrangements, maintains proper telomere length regulation, helps repairing DNA damage created by a number of genotoxins and participates in sister chromatid cohesion. Elg1 is evolutionarily conserved, and its Fanconi Anemia-related mammalian ortholog (also known as ATAD5) is embryonic lethal when lost in mice and acts as a tumor suppressor in mice and humans. Elg1 encodes a protein that forms an RFC-like complex that unloads the replicative clamp, PCNA, from DNA, mainly in its SUMOylated form. We have identified 2 different regions in yeast Elg1 that undergo phosphorylation. Phosphorylation of one of them, S112, is dependent on the ATR yeast ortholog, Mec1, and probably is a direct target of this kinase. We show that phosphorylation of Elg1 is important for its role at telomeres. Mutants unable to undergo phosphorylation suppress the DNA damage sensitivity of Drad5 mutants, defective for an error-free post-replicational bypass pathway. This indicates a role of phosphorylation in the regulation of DNA repair. Our results open the way to investigate the mechanisms by which the activity of Elg1 is regulated during DNA replication and in response to DNA damage.

Original languageEnglish
Pages (from-to)3689-3697
Number of pages9
JournalCell Cycle
Volume14
Issue number23
DOIs
StatePublished - 1 Jan 2015

Funding

FundersFunder number
Israel Cancer Research Foundation
Israel Cancer Association
Israel Science Foundation

    Keywords

    • ATM/Tel1
    • Atr/Mec1
    • DNA damage response
    • DNA repair
    • DNA replication
    • Telomeres

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