Base excision repair of oxidative DNA damage activated by XPG protein

Oxidized pyrimidines in DNA are removed by a distinct base excision repair pathway initiated by the DNA glycosylase-AP lyase hNth1 in human cells. We have reconstituted this single-residue replacement pathway with recombinant proteins, including the AP endonuclease HAP1/APE, DNA polymerase beta, and DNA ligase III-XRCC1 heterodimer. With these proteins, the nucleotide exci sion repair enzyme XPG serves as a cofactor for the efficient function of h Nth1. XPG protein promotes binding of hNth1 to damaged DNA. The stimulation of hNth1 activity is retained in XPG catalytic site mutants inactive in nu cleotide excision repair. The data support the model that development of Co ckayne syndrome in XP-G patients is related to inefficient excision of endo genous oxidative DNA damage.