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

Claudia M. Nicolae | Zendy; Erin R. Aho | Zendy; Katherine N. Choe | Zendy; Daniel Constantin | Zendy; He-Juan Hu | Zendy; Deokjae Lee | Zendy; Kyungjae Myung | Zendy; GeorgeLucian Moldovan | Zendy

Open Access

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

Author(s) -

Claudia M. Nicolae,

Erin R. Aho,

Katherine N. Choe,

Daniel Constantin,

He-Juan Hu,

Deokjae Lee,

Kyungjae Myung,

GeorgeLucian Moldovan

Publication year - 2015

Publication title -

nucleic acids research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 9.008

H-Index - 537

eISSN - 1362-4954

pISSN - 0305-1048

DOI - 10.1093/nar/gkv147

Subject(s) - biology , rad51 , homologous recombination , replication protein a , dna repair , dna replication , genome instability , postreplication repair , homology directed repair , replication factor c , dna , eukaryotic dna replication , proliferating cell nuclear antigen , dna damage , control of chromosome duplication , microbiology and biotechnology , genetics , dna mismatch repair , gene , dna binding protein , transcription factor

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.

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