The yeast pcna unloader Elg1 RFC-like complex plays a role in eliciting the DNA damage checkpoint

Soumitra Sau, Batia Liefshitz, Martin Kupiec*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The PCNA (proliferating cell nuclear antigen) ring plays central roles during DNA replication and repair. The yeast Elg1 RFC-like complex (RLC) is the principal unloader of chromatin-bound PCNA and thus plays a central role in maintaining genome stability. Here we identify a role for Elg1 in the unloading of PCNA during DNA damage. Using DNA damage checkpoint (DC)-inducible and replication checkpoint (RC)-inducible strains, we show that Elg1 is essential for eliciting the signal in the DC branch. In the absence of Elg1 activity, the Rad9 (53BP1) and Dpb11 (TopBP1) adaptor proteins are recruited but fail to be phosphorylated by Mec1 (ATR), resulting in a lack of checkpoint activation. The chromatin immunoprecipita-tion of PCNA at the Lac operator sites reveals that accumulated local PCNA influences the checkpoint activation process in elg1 mutants. Our data suggest that Elg1 participates in a mechanism that may coordinate PCNA unloading during DNA repair with DNA damage checkpoint induction. IMPORTANCE The Elg1protein forms an RFC-like complex in charge of unloading PCNA from chromatin during DNA replication and repair. Mutations in the ELG1 gene caused genomic instability in all organisms tested and cancer in mammals. Here we show that Elg1 plays a role in the induction of the DNA damage checkpoint, a cellular response to DNA damage. We show that this defect is due to a defect in the signal amplification process during induction. Thus, cells coordinate the cell’s response and the PCNA unloading through the activity of Elg1.

Original languageEnglish
Article numbere01159-19
JournalmBio
Volume10
Issue number3
DOIs
StatePublished - 1 May 2019

Funding

FundersFunder number
Israel Cancer Research Fund
Department of Biotechnology, Ministry of Science and Technology, India
Volkswagen Foundation
Israel Science Foundation

    Keywords

    • DNA damage checkpoint
    • DNA repair
    • DNA replication
    • Dpb11
    • PCNA
    • RFC-like complex
    • Rad9
    • Saccharomyces cerevisiae
    • Yeast

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