title: XPG endonuclease makes the 3' incision in human DNA nucleotide excision repair.
abstract: Humans with a defect in the XPG protein suffer from xeroderma pigmentosum (XP) resulting from an inability to perform DNA nucleotide excision repair properly. Here we show that XPG makes a structure-specific endonucleolytic incision in a synthetic DNA substrate containing a duplex region and single-stranded arms. One strand of the duplex is cleaved at the border with single-stranded DNA. A cut with the same polarity is also made in a bubble structure, at the 3' side of the centrally unpaired region. Normal cell extracts introduce a nick 3' to a platinum-DNA lesion, but an XP-G cell extract is defective in making this incision. These data show that XPG has a direct role in making one of the incisions required to excise a damaged oligonucleotide, by cleaving 3' to DNA damage during nucleotide excision repair.
authors.affiliation: Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, UK.
authors.forename: A
authors.initials: A
authors.lastname: O'Donovan
authors.forename: A A
authors.initials: AA
authors.lastname: Davies
authors.forename: J G
authors.initials: JG
authors.lastname: Moggs
authors.forename: S C
authors.initials: SC
authors.lastname: West
authors.forename: R D
authors.initials: RD
authors.lastname: Wood
mesh_terms: D001483:Base Sequence; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D004720:Endonucleases / Q000378:metabolism*; D004926:Escherichia coli; D005656:Fungal Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins; D014983:Xeroderma Pigmentosum / Q000201:enzymology* / Q000235:genetics
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C073998:RAD2 protein, S cerevisiae; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C023141:DNA-specific endonuclease (xeroderma pigmentosum)