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Mol Cell. 2012 Jan 13;45(1):75-86. doi: 10.1016/j.molcel.2011.11.010. Epub 2011 Dec 6.

Inhibition of homologous recombination by the PCNA-interacting protein PARI.

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1
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

Abstract

Inappropriate homologous recombination (HR) causes genomic instability and cancer. In yeast, the UvrD family helicase Srs2 is recruited to sites of DNA replication by SUMO-modified PCNA, where it acts to restrict HR by disassembling toxic RAD51 nucleofilaments. How human cells control recombination at replication forks is unknown. Here, we report that the protein PARI, containing a UvrD-like helicase domain, is a PCNA-interacting partner required for preservation of genome stability in human and DT40 chicken cells. Using cell-based and biochemical assays, we show that PARI restricts unscheduled recombination by interfering with the formation of RAD51-DNA HR structures. Finally, we show that PARI knockdown suppresses the genomic instability of Fanconi Anemia/BRCA pathway-deficient cells. Thus, we propose that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks.

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PMID:
22153967
PMCID:
PMC3267324
DOI:
10.1016/j.molcel.2011.11.010
[Indexed for MEDLINE]
Free PMC Article

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