The ADP-ribosyltransferase PARP10/ARTD10 interacts with proliferating cell nuclear antigen (PCNA) and is required for DNA damage tolerance.
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.
From the Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033.
Claudia M
CM
Nicolae
Erin R
ER
Aho
Alexander H S
AH
Vlahos
Katherine N
KN
Choe
Subhajyoti
S
De
Georgios I
GI
Karras
George-Lucian
GL
Moldovan
D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation
D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; C499627:PARP10 protein, human; D011065:Poly(ADP-ribose) Polymerases; D004259:DNA-Directed DNA Polymerase
ADP-ribosylation; DNA Damage; DNA Repair; DNA Replication; Genomic Instability; PCNA; Translesion Synthesis