The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η

@article{Masutani1999TheX,
  title={The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase $\eta$},
  author={Chikahide Masutani and Rika Kusumoto and Ayumi Yamada and Naoshi Dohmae and Masayuki Yokoi and Mayumi Yuasa and Marito Araki and Shigenori Iwai and Koji Takio and Fumio Hanaoka},
  journal={Nature},
  year={1999},
  volume={399},
  pages={700-704}
}
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… 

Molecular genetics of Xeroderma pigmentosum variant

Identification of POLH as the XPV gene provides an important instrument for improving molecular diagnostics in XPV families, confirming the autosomal recessive nature of the condition.

Molecular analysis of mutations in DNA polymerase η in xeroderma pigmentosum-variant patients

It is anticipated that protein in XP-V cells will not be localized in the nucleus nor will it be relocalized into replication foci during DNA replication, and the spectrum of both missense and truncating mutations is markedly skewed toward the N-terminal half of the protein.

Spotlight on 'xeroderma pigmentosum'.

  • H. Fassihi
  • Medicine, Biology
    Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology
  • 2013
The study of patients with XP has highlighted the importance of nucleotide excision repair in the aetiology of skin cancers and neurological degeneration, and has solidified the link between UV exposure, DNA damage, somatic mutations and skin cancer.

Variant subtype of xeroderma pigmentosum with multiple basal cell carcinomas diagnosed in a Chinese woman

The application of dermatoscopy was important to early diagnosis and treatment of accompanied skin cancers and then improve the prognosis of this disease.

Genetic correction of DNA repair-deficient/cancer-prone xeroderma pigmentosum group C keratinocytes.

It is demonstrated that DNA repair capacity, cell survival properties, and transition from proliferative to abortive keratinocyte colonies toward UVB irradiation can be fully recovered in keratinocytes from patients with XPC transduced with a retroviral vector stably driving the expression of the wild-type XPC protein.

Polymerase eta deficiency in the xeroderma pigmentosum variant uncovers an overlap between the S phase checkpoint and double-strand break repair.

It is identified that XPV cells make use of a homologous recombination pathway involving the hMre11/hRad50/Nbs1 protein complex, but not the Rad51 recombination pathways, which may be associated with increased genomic rearrangements that result from double-strand breakage and rejoining in cells of the skin.

Complementation of the DNA repair deficiency in human xeroderma pigmentosum group a and C cells by recombinant adenovirus-mediated gene transfer.

Rec recombinant adenoviruses carrying the XPA and XPC genes that were used to infect XP-A and XP-C immortalized and primary fibroblast cell lines confirmed complete phenotypic reversion in XP DNA repair deficient cells with no trace of cytotoxicity.

Complementation of defective translesion synthesis and UV light sensitivity in xeroderma pigmentosum variant cells by human and mouse DNA polymerase

The results suggest that DNA polymerase eta plays a role in DNA replication, though the enzyme is not essential for viability.

Adenovirus mediated transduction of the human DNA polymerase eta cDNA.

...

References

SHOWING 1-10 OF 23 REFERENCES

Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation.

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.

Defective bypass replication of a leading strand cyclobutane thymine dimer in xeroderma pigmentosum variant cell extracts.

The bypass replication defect of XP-V may represent a novel category of hereditary mutator phenotypes affecting DNA damage processing, and the disease extracts were as competent as controls for replication of the undamaged TT plasmid and for leading T x T-induced fork uncoupling.

Xeroderma pigmentosum variant cells are less likely than normal cells to incorporate dAMP opposite photoproducts during replication of UV-irradiated plasmids.

Transfecting an XP variant cell line with a UV-irradiated shuttle vector carrying the supF gene as a target for mutations determined the frequency and spectrum of mutations induced, and compared the results with those obtained when irradiated plasmids carrying the same target gene replicated in a normal cell line suggested that XP variant cells are less likely than normal cells to incorporate dAMP opposite bases involved in photo-products.

Impaired Translesion Synthesis in Xeroderma Pigmentosum Variant Extracts

It is demonstrated unequivocally that the defect in XPV cells resides in translesion synthesis independently of the slippage process, and normal extracts were able to perform TLS 10-fold more efficiently than XPV extracts.

Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts

It is suggested that XP variant cells are much less likely than normal cells to incorporate either dAMP or dGMP opposite the pyrimidines involved in photoproducts, which would account for their significantly higher frequency of mutants and might explain their abnormal delay in replicating a UV-damaged template.

Abnormal, Error-Prone Bypass of Photoproducts by Xeroderma Pigmentosum Variant Cell Extracts Results in Extreme Strand Bias for the Kinds of Mutations Induced by UV Light

The data indicate that the UV hypermutability of XP variant cells results from reduced bypass fidelity and that unlike for normal cells, bypass of photoproducts involving cytosine in the template for the leading strand differs significantly from that of photocts in the lagging strand.

Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23.

The purification to homogeneity and subsequent cDNA cloning of a repair complex by in vitro complementation of the XP‐C defect in a cell‐free repair system containing UV‐damaged SV40 minichromosomes implies that the complex exerts a unique function in the genome‐overall repair pathway which is important for prevention of skin cancer.

Identification, chromosomal mapping and tissue-specific expression of hREV3 encoding a putative human DNA polymerase zeta.

Results indicate that mammalian cells may also contain a mutagenic pathway which aids in cell survival at the cost of increased mutation.

Deoxycytidyl transferase activity of yeast REV1 protein

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.