Micronuclei in EM9 cells expressing polymorphic forms of human XRCC1

X-ray repair cross-complementing gene 1 (XRCC1) is involved in base excision repair (BER) through interaction with other BER enzymes, and polymorphisms in XRCC1 appear to increase the risk of various cancers. We evaluated how three XRCC1 polymorphisms, Arg194Trp, Arg280His and Arg399Gln, affect the extent of DNA damage and repair using the micronucleus assay. XRCC1 cDNAs containing the wild-type sequence and the three polymorphisms were overexpressed in EM9 cells, which lack the full sequence needed to perform XRCC1 functions. Normal human XRCC1 cDNA corrected the defect in EM9 cells. Only XRCC1 cDNA containing the Arg399Gln polymorphism did not fully correct the DNA repair defect in EM9 cells. These results indicate that the Arg399Gln polymorphism, but not the Arg194Trp or Arg280His polymorphism, influences the ability of XRCC1 to repair DNA. This study may provide a model that can be used to evaluate the functional significance of polymorphisms in DNA repair genes.