XPG endonuclease makes the 3′ incision in human DNA nucleotide excision repair

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Abstract
HUMANS with a defect in the XPG protein suffer from xeroderma pigmentosum (XP) resulting from an inability to perform DNA nucleotide excision repair properly1–4. 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.