Ghosal G, Leung JW, Nair BC, Fong KW, Chen J

DNA damage-induced PCNA ubiquitination serves as the key event mediating post-replication repair (PRR). PRR 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 colocalizes and interacts with unmodified and ubiquitinated PCNA (Ub-PCNA) at ...

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UV induced damage sites, which require the PIP box and UBZ domain of C1orf124. C1orf124 also binds to AAA ATPase VCP via its SHP domain and cellular resistance to UV radiation mediated by C1orf124 requires its interactions with VCP and PCNA. Interestingly, C1orf124 binds to replicative DNA polymerase POLD3 and PDIP1 (POLD3 interacting protein 1) under normal conditions, but preferentially associates with TLS polymerase POL η (POL eta/POL H) upon UV damage. Depletion of C1orf124 compromised PCNA monoubiquitination, RAD18 chromatin association and RAD18 localization to UV damage sites. Thus, C1orf124 acts at multiple steps in TLS, stabilizes RAD18 and Ub-PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion.

Date: Aug. 17, 2012

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