Mammalian polymerase zeta is essential for post-replication repair of UV-induced DNA lesions.
DNA polymerase zeta is believed to be an essential constituent of DNA damage tolerance, comprising several pathways that allow the replication of DNA templates containing unrepaired damage. We wanted to better define the role of polymerase zeta in DNA damage tolerance in mammalian cells. To this aim we have investigated replication of ultraviolet light-damaged DNA templates in mouse embryonic fibroblasts deficient for Rev3, the catalytic subunit of polymerase zeta. We found that Rev3 is important for a post-replication repair pathway of helix-distorting [6-4]pyrimidine-pyrimidone photoproducts and, to a lesser extent, of cyclobutane pyrimidine dimers. Unlike its partner Rev1, Rev3 appears not to be involved in an immediate translesion synthesis pathway at a stalled replication fork. The deficiency of Rev3(-/-) MEFs in post-replication repair of different photoproducts contributes to the extreme sensitivity of these cells to UV light.
Jansen
Jacob G
JG
Department of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, PO Box 9600, 2300 RC Leiden, The Netherlands.
Tsaalbi-Shtylik
Anastasia
A
Hendriks
Giel
G
Verspuy
Johan
J
Gali
Himabindu
H
Haracska
Lajos
L
de Wind
Niels
N
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014466:Ultraviolet Rays
D004247:DNA; D004259:DNA-Directed DNA Polymerase; C425929:DNA polymerase zeta; C486862:REV3L protein, mouse