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

Claudia M. Nicolae, Erin R. Aho, Katherine N. Choe, Daniel Constantin, He Juan Hu, Deokjae Lee, Kyungjae Myung, George Lucian Moldovan

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 posttranslational modification playing a prominent role in DNA repair, but much less is known about mono- ADP-ribosylation. Here we report that mono-ADPribosylation 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.

Original languageEnglish (US)
Pages (from-to)3143-3153
Number of pages11
JournalNucleic acids research
Volume43
Issue number6
DOIs
StatePublished - Jan 1 2015

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ADP Ribose Transferases
Homologous Recombination
DNA Repair
Genomic Instability
Post Translational Protein Processing
DNA Replication
Adenosine Diphosphate
Recombinational DNA Repair
DNA Breaks
Proliferating Cell Nuclear Antigen
DNA Damage
Hypersensitivity
DNA
Neoplasms

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Nicolae, Claudia M. ; Aho, Erin R. ; Choe, Katherine N. ; Constantin, Daniel ; Hu, He Juan ; Lee, Deokjae ; Myung, Kyungjae ; Moldovan, George Lucian. / A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting homologous recombination and protecting against replication stress. In: Nucleic acids research. 2015 ; Vol. 43, No. 6. pp. 3143-3153.
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A novel role for the mono-ADP-ribosyltransferase PARP14/ARTD8 in promoting homologous recombination and protecting against replication stress. / Nicolae, Claudia M.; Aho, Erin R.; Choe, Katherine N.; Constantin, Daniel; Hu, He Juan; Lee, Deokjae; Myung, Kyungjae; Moldovan, George Lucian.

In: Nucleic acids research, Vol. 43, No. 6, 01.01.2015, p. 3143-3153.

Research output: Contribution to journalArticle

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