Proliferating Cell Nuclear Antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis

Gargi Ghosal, Justin Wai Chung Leung, Binoj C. Nair, Ka Wing Fong, Junjie Chen

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

DNA damage-induced proliferating cell nuclear antigen (PCNA) ubiquitination serves as the key event mediating post-replication repair. Post-replication repair involves either translesion synthesis (TLS) or damage avoidance via template switching. In this study, we have identified and characterized C1orf124 as a regulator of TLS. C1orf124 co-localizes and interacts with unmodified and mono-ubiquitinated PCNA at UV light-induced damage sites, which require the PIP box and UBZ domain of C1orf124. C1orf124 also binds to the AAA-ATPase valosin-containing protein via its SHP domain, and cellular resistance to UV radiation mediated by C1orf124 requires its interactions with valosin-containing protein and PCNA. Interestingly, C1orf124 binds to replicativeDNApolymerase POLD3 and PDIP1 under normal conditions but preferentially associates with TLS polymerase η (POLH) upon UV damage. Depletion of C1orf124 compromises PCNA monoubiquitination, RAD18 chromatin association, and RAD18 localization to UV damage sites. Thus, C1orf124 acts at multiple steps in TLS, stabilizes RAD18 and ubiquitinated PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion.

Original languageEnglish (US)
Pages (from-to)34225-34233
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number41
DOIs
StatePublished - Oct 5 2012

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Proliferating Cell Nuclear Antigen
Carrier Proteins
Ultraviolet radiation
Repair
Ubiquitination
DNA
Ultraviolet Rays
DNA Damage
Chromatin
Adenosine Triphosphatases
Switches
Association reactions
Radiation
CDC48 protein

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Proliferating Cell Nuclear Antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis. / Ghosal, Gargi; Leung, Justin Wai Chung; Nair, Binoj C.; Fong, Ka Wing; Chen, Junjie.

In: Journal of Biological Chemistry, Vol. 287, No. 41, 05.10.2012, p. 34225-34233.

Research output: Contribution to journalArticle

Ghosal, Gargi ; Leung, Justin Wai Chung ; Nair, Binoj C. ; Fong, Ka Wing ; Chen, Junjie. / Proliferating Cell Nuclear Antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 41. pp. 34225-34233.
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