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Nucleic Acids Res. 2015 Mar 31;43(6):3143-53. doi: 10.1093/nar/gkv147. Epub 2015 Mar 9.

A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting homologous recombination and protecting against replication stress.

Author information

1
Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
2
Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA Suzhou Health College, Suzhou, Jiangsu 215009, P.R. China.
3
Genome Instability Section, National Human Genome Research Institute, Bethesda, MD 20892, USA.
4
Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA gmoldovan@hmc.psu.edu.

Abstract

Genomic instability, a major hallmark of cancer cells, is caused by incorrect or ineffective DNA repair. Many DNA repair mechanisms cooperate in cells to fight DNA damage, and are generally regulated by post-translational modification of key factors. Poly-ADP-ribosylation, catalyzed by PARP1, is a post-translational modification playing a prominent role in DNA repair, but much less is known about mono-ADP-ribosylation. Here we report that mono-ADP-ribosylation plays an important role in homologous recombination DNA repair, a mechanism essential for replication fork stability and double strand break repair. We show that the mono-ADP-ribosyltransferase PARP14 interacts with the DNA replication machinery component PCNA and promotes replication of DNA lesions and common fragile sites. PARP14 depletion results in reduced homologous recombination, persistent RAD51 foci, hypersensitivity to DNA damaging agents and accumulation of DNA strand breaks. Our work uncovered PARP14 as a novel factor required for mitigating replication stress and promoting genomic stability.

PMID:
25753673
PMCID:
PMC4381061
DOI:
10.1093/nar/gkv147
[Indexed for MEDLINE]
Free PMC Article

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