Journal ArticleDOI
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.
Chikahide Masutani,Rika Kusumoto,Rika Kusumoto,Ayumi Yamada,Naoshi Dohmae,Masayuki Yokoi,Mayumi Yuasa,Marito Araki,Shigenori Iwai,Koji Takio,Fumio Hanaoka +10 more
TLDR
Recombinant human DNA polymerase η corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA, indicating that DNA polymerases η could be the XPV gene product.Abstract:
Xeroderma pigmentosum variant (XP-V) is an inherited disorder which is associated with increased incidence of sunlight-induced skin cancers. Unlike other xeroderma pigmentosum cells (belonging to groups XP-A to XP-G), XP-V cells carry out normal nucleotide-excision repair processes but are defective in their replication of ultraviolet-damaged DNA. It has been suspected for some time that the XPV gene encodes a protein that is involved in trans-lesion DNA synthesis, but the gene product has never been isolated. Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts. Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase eta. This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. We found that all XP-V cells examined carry mutations in their DNA polymerase eta gene. Recombinant human DNA polymerase eta corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. Together, these results indicate that DNA polymerase eta could be the XPV gene product.read more
Citations
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sources and effects of ionizing radiation
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Journal ArticleDOI
Genome maintenance mechanisms for preventing cancer
TL;DR: This review summarizes the main DNA caretaking systems and their impact on genome stability and carcinogenesis.
Journal ArticleDOI
Quality control by DNA repair.
Tomas Lindahl,Richard D. Wood +1 more
TL;DR: In some cases, DNA damage is not repaired but is instead bypassed by specialized DNA polymerases, and the integrity of the genetic information is compromised.
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Proliferating cell nuclear antigen (PCNA): a dancer with many partners.
Giovanni Maga,Ulrich Hübscher +1 more
TL;DR: Structural and biochemical studies are starting to provide a first glimpse of how both PCNA temporally and spatially organise their functions and how both tasks can be achieved.
Journal ArticleDOI
Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers
Gerd P. Pfeifer,Mikhail F. Denissenko,Magali Olivier,Natalia Y. Tretyakova,Stephen S. Hecht,Pierre Hainaut +5 more
TL;DR: The available data suggest that p53 mutations in lung cancers can be attributed to direct DNA damage from cigarette smoke carcinogens rather than to selection of pre-existing endogenous mutations.
References
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Book
DNA Repair and Mutagenesis
TL;DR: Nucleotide excision repair in mammalian cells: genes and proteins Mismatch repair The SOS response and recombinational repair in prokaryotes Mutagenesis in proKaryote Mutagenisation in eukaryotes Other DNA damage tolerance responses in eUKaryotes.
Journal ArticleDOI
Efficient Bypass of a Thymine-Thymine Dimer by Yeast DNA Polymerase, Polη
TL;DR: The RAD30 gene of the yeast Saccharomyces cerevisiae is shown to encode a DNA polymerase that can replicate efficiently past a thymine-thymine cis-syn cyclobutane dimer, a lesion that normally blocks DNA polymerases.
Journal ArticleDOI
Thymine-Thymine Dimer Bypass by Yeast DNA Polymerase ζ
TL;DR: The REV3 and REV7 genes of the yeast Saccharomyces cerevisiae are required for DNA damage-induced mutagenesis and the Rev3 and Rev7 proteins were shown to form a complex with DNA polymerase activity, which is the sixth eukaryoticDNA polymerase to be described, and is therefore called DNA polymerases ζ.
Journal ArticleDOI
Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation.
Alan R. Lehmann,S. Kirk-Bell,Colin F. Arlett,M. C. Paterson,P. H. M. Lohman,E. A. de Weerd-Kastelein,Dirk Bootsma +6 more
TL;DR: Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.
Journal ArticleDOI
Deoxycytidyl transferase activity of yeast REV1 protein
TL;DR: It is shown here that Revl protein has a deoxycytidyl transferase activity which transfers a dCMP residue from dCTP to the 3′ end of a DNA primer in a template-dependent reaction.