1. Academic Validation
  2. The ADP-ribosyltransferase PARP10/ARTD10 interacts with proliferating cell nuclear antigen (PCNA) and is required for DNA damage tolerance

The ADP-ribosyltransferase PARP10/ARTD10 interacts with proliferating cell nuclear antigen (PCNA) and is required for DNA damage tolerance

  • J Biol Chem. 2014 May 9;289(19):13627-37. doi: 10.1074/jbc.M114.556340.
Claudia M Nicolae 1 Erin R Aho Alexander H S Vlahos Katherine N Choe Subhajyoti De Georgios I Karras George-Lucian Moldovan
Affiliations

Affiliation

  • 1 From the Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033.
Abstract

All cells rely on genomic stability mechanisms to protect against DNA alterations. PCNA is a master regulator of DNA replication and S-phase-coupled repair. PCNA post-translational modifications by ubiquitination and SUMOylation dictate how cells stabilize and re-start replication forks stalled at sites of damaged DNA. PCNA mono-ubiquitination recruits low fidelity DNA polymerases to promote error-prone replication across DNA lesions. Here, we identify the mono-ADP-ribosyltransferase PARP10/ARTD10 as a novel PCNA binding partner. PARP10 knockdown results in genomic instability and DNA damage hypersensitivity. Importantly, we show that PARP10 binding to PCNA is required for translesion DNA synthesis. Our work identifies a novel PCNA-linked mechanism for genome protection, centered on post-translational modification by mono-ADP-ribosylation.

Keywords

ADP-ribosylation; DNA Damage; DNA Repair; DNA Replication; Genomic Instability; PCNA; Translesion Synthesis.

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