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.
Johnson, C., Gali, V. K., Takahashi, T. S., & Kubota, T. (2016). PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1. Cell Reports, 16(3), 684-695. https://doi.org/10.1016/j.celrep.2016.06.030