PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1
書誌事項
- 公開日
- 2016-07
- 資源種別
- journal article
- 権利情報
-
- https://www.elsevier.com/tdm/userlicense/1.0/
- https://www.elsevier.com/legal/tdmrep-license
- http://creativecommons.org/licenses/by/4.0/
- DOI
-
- 10.1016/j.celrep.2016.06.030
- 公開者
- Elsevier BV
この論文をさがす
説明
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.
収録刊行物
-
- Cell Reports
-
Cell Reports 16 (3), 684-695, 2016-07
Elsevier BV
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キーワード
- DNA Replication
- G2 Phase
- Saccharomyces cerevisiae Proteins
- Supplementary Data
- QH301-705.5
- Saccharomyces cerevisiae
- R Medicine
- Article
- Genomic Instability
- SDG 3 - Good Health and Well-being
- Proliferating Cell Nuclear Antigen
- Biology (General)
- Replication Protein C
- DNA, Fungal
- L019698/1
- R
- K006304/1
- Medical Research Council (MRC)
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Carrier Proteins
- Cell Division
