Requirement of DNA polymerase eta for error-free bypass of UV-induced CC and TC photoproducts.
The yeast RAD30-encoded DNA polymerase eta (Poleta) bypasses a cis-syn thymine-thymine dimer efficiently and accurately. Human DNA polymerase eta functions similarly in the bypass of this lesion, and mutations in human Poleta result in the cancer prone syndrome, the variant form of xeroderma pigmentosum. UV light, however, also elicits the formation of cis-syn cyclobutane dimers and (6-4) photoproducts at 5'-CC-3' and 5'-TC-3' sites, and in both yeast and human DNA, UV-induced mutations occur primarily by 3' C to T transitions. Genetic studies presented here reveal a role for yeast Poleta in the error-free bypass of cyclobutane dimers and (6-4) photoproducts formed at CC and TC sites. Thus, by preventing UV mutagenesis at a wide spectrum of dipyrimidine sites, Poleta plays a pivotal role in minimizing the incidence of sunlight-induced skin cancers in humans.
Yu
S L
SL
Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555-1061, USA.
Johnson
R E
RE
Prakash
S
S
Prakash
L
L
D000483:Alleles; D001483:Base Sequence; D002455:Cell Division / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D016296:Mutagenesis / Q000235:genetics / Q000528:radiation effects; D011740:Pyrimidine Dimers / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D017422:Sequence Analysis, DNA; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics; D015003:Yeasts / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000528:radiation effects; D000099270:Y-Family DNA Polymerases
D004259:DNA-Directed DNA Polymerase; D011740:Pyrimidine Dimers; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases