PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1

Catherine Johnson, Vamsi K. Gali, Tatsuro Takahashi, Takashi Kubota

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Loss of the genome maintenance factor Elg1 causes serious genome instability that leads to cancer, but the underlying mechanism is unknown. Elg1 forms the major subunit of a replication factor C-like complex, Elg1-RLC, which unloads the ring-shaped polymerase clamp PCNA from DNA during replication. Here, we show that prolonged retention of PCNA on DNA into G2/M phase is the major cause of genome instability in elg1Δ yeast. Overexpression-induced accumulation of PCNA on DNA causes genome instability. Conversely, disassembly-prone PCNA mutants that relieve PCNA accumulation rescue the genome instability of elg1Δ cells. Covalent modifications to the retained PCNA make only a minor contribution to elg1Δ genome instability. By engineering cell-cycle-regulated ELG1 alleles, we show that abnormal accumulation of PCNA on DNA during S phase causes moderate genome instability and its retention through G2/M phase exacerbates genome instability. Our results reveal that PCNA unloading by Elg1-RLC is critical for genome maintenance.

Original languageEnglish
Pages (from-to)684-695
Number of pages12
JournalCell Reports
Volume16
Issue number3
DOIs
Publication statusPublished - Jul 19 2016

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Genomic Instability
G2 Phase
Proliferating Cell Nuclear Antigen
Cell Division
Genes
DNA
Replication Protein C
Maintenance
Genome
Cell engineering
DNA Replication
S Phase
Clamping devices
Unloading
Yeast
Cell Cycle
Yeasts
Alleles

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1. / Johnson, Catherine; Gali, Vamsi K.; Takahashi, Tatsuro; Kubota, Takashi.

In: Cell Reports, Vol. 16, No. 3, 19.07.2016, p. 684-695.

Research output: Contribution to journalArticle

Johnson, Catherine ; Gali, Vamsi K. ; Takahashi, Tatsuro ; Kubota, Takashi. / PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1. In: Cell Reports. 2016 ; Vol. 16, No. 3. pp. 684-695.
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