DNA Ligases I and III Support Nucleotide Excision Repair in DT40 Cells with Similar Efficiency.

Autor: Paul-Konietzko K; Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, Germany., Thomale J; Institute of Cell Biology, University of Duisburg-Essen Medical School, Essen, Germany., Arakawa H; Institute for Radiocytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Iliakis G; Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Essen, Germany.
Jazyk: angličtina
Zdroj: Photochemistry and photobiology [Photochem Photobiol] 2015 Sep-Oct; Vol. 91 (5), pp. 1173-80. Date of Electronic Publication: 2015 Aug 03.
DOI: 10.1111/php.12487
Abstrakt: In eukaryotic cells helix-distorting DNA lesions like cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidone photoproducts (6-4 PPs) are efficiently removed by nucleotide excision repair (NER). NER is a multistep process where in the end, subsequent to replication over the gap, the remaining nick is sealed by a DNA ligase. Lig1 has been implicated as the major DNA ligase in NER. Recently, Lig3 has been implicated as a component of a NER subpathway that operates in dividing cells, but which becomes particularly important in nondividing cells. Here, we use DT40 cells and powerful gene targeting approaches for generating DNA ligase mutants to examine the involvement and contribution of Lig1 and Lig3 in NER using cell survival measured by colony formation, and repair kinetics of CPD by immunofluorescence microscopy and immuno-slot-blotting. Our results demonstrate an impressive and previously undocumented potential of Lig3 to substitute for Lig1 in removing helix-distorting DNA lesions by NER in proliferating cells. We show for the first time in a clean genetic background a functional redundancy in NER between Lig1 and Lig3, which appears to be cell cycle independent and which is likely to contribute to the stability of vertebrate genomes.
(© 2015 The American Society of Photobiology.)
Databáze: MEDLINE
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