Unknown

Dataset Information

0

FF483-484 motif of human Pol? mediates its interaction with the POLD2 subunit of Pol? and contributes to DNA damage tolerance.


ABSTRACT: Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase ? (Pol?) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Pol? deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrome, characterized by a predisposition to skin cancer. Here, we show that the FF483-484 amino acids in the human Pol? (designated F1 motif) are necessary for the interaction of this TLS polymerase with POLD2, the B subunit of the replicative DNA polymerase ?, both in vitro and in vivo. Mutating this motif impairs Pol? function in the bypass of both an N-2-acetylaminofluorene adduct and a TT-CPD lesion in cellular extracts. By complementing XPV cells with different forms of Pol?, we show that the F1 motif contributes to the progression of DNA synthesis and to the cell survival after UV irradiation. We propose that the integrity of the F1 motif of Pol?, necessary for the Pol?/POLD2 interaction, is required for the establishment of an efficient TLS complex.

SUBMITTER: Baldeck N 

PROVIDER: S-EPMC4344513 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

FF483-484 motif of human Polη mediates its interaction with the POLD2 subunit of Polδ and contributes to DNA damage tolerance.

Baldeck Nadège N   Janel-Bintz Régine R   Wagner Jérome J   Tissier Agnès A   Fuchs Robert P RP   Burkovics Peter P   Haracska Lajos L   Despras Emmanuelle E   Bichara Marc M   Chatton Bruno B   Cordonnier Agnès M AM  

Nucleic acids research 20150206 4


Switching between replicative and translesion synthesis (TLS) DNA polymerases are crucial events for the completion of genomic DNA synthesis when the replication machinery encounters lesions in the DNA template. In eukaryotes, the translesional DNA polymerase η (Polη) plays a central role for accurate bypass of cyclobutane pyrimidine dimers, the predominant DNA lesions induced by ultraviolet irradiation. Polη deficiency is responsible for a variant form of the Xeroderma pigmentosum (XPV) syndrom  ...[more]

Similar Datasets

| S-EPMC8698299 | biostudies-literature
| S-EPMC121423 | biostudies-literature
| S-EPMC7437177 | biostudies-literature
| S-EPMC5352485 | biostudies-literature
| S-EPMC5935547 | biostudies-literature
| S-EPMC4898654 | biostudies-literature
| S-EPMC3766730 | biostudies-literature
| S-EPMC3753651 | biostudies-literature
| S-EPMC8527527 | biostudies-literature
| S-EPMC9304150 | biostudies-literature