title: The RAD30 cancer susceptibility gene.
abstract: The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in RAD30, which encodes the novel lesion bypass DNA polymerase eta. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV irradiation. In cell-free extracts of XPV lymphoblasts, functional DNA polymerase eta is required for the complete replication of a double-stranded plasmid containing either a single (6-4) photoproduct or a cyclobutane pyrimidine dime(CPD), the major mutagenic UV-induced lesion. In cultured XPV cells, replication arrest activates downstream signalling pathways, leading to hyperphosphorylation of the 34-kDa subunit of the trimeric single-stranded DNA-binding protein, RPA (replication protein A). Many of the RAD30 mutations identified in XPV cells result in truncation and inactivation of DNA polymerase eta. To examine whether polymorphisms in the RAD30 gene that result in altered polymerase eta function, rather than enzyme inactivation, might contribute to individual susceptibility to skin cancer, methods to screen for sequence changes in the RAD30 gene in human genomic DNAhave been developed.
authors.affiliation: Department of Biochemistry, National University of Ireland, Galway, Ireland. michael.carty@nuigalway.ie
authors.forename: M P
authors.initials: MP
authors.lastname: Carty
authors.forename: M
authors.initials: M
authors.lastname: Glynn
authors.forename: M
authors.initials: M
authors.lastname: Maher
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Yao
authors.forename: K
authors.initials: K
authors.lastname: Dixon
authors.forename: J
authors.initials: J
authors.lastname: McCann
authors.forename: L
authors.initials: L
authors.lastname: Rynn
authors.forename: A
authors.initials: A
authors.lastname: Flanagan
mesh_terms: D000818:Animals; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010766:Phosphorylation; D012878:Skin Neoplasms / Q000235:genetics; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases