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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)
8 Downloads (Pure)

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 ringshaped 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
Early online date30 Jun 2016
DOIs
Publication statusPublished - 19 Jul 2016

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