We study DNA damage and repair in higher eukaryotes, focusing on base excision repair. This repair mechanism serves for various damaged bases, abasic sites, and single-strand breaks, which are the most abundant types of lesions generated during normal cellular metabolism and also induced by some treatments such as ionizing radiation and alkylating agents. In higher eukayotes, base excision repair can proceed by two alternative pathways: a proliferating cell nuclear antigen (PCNA)-dependent pathway and a DNA polymerase b (pol b)-dependent pathway. We are currently investigating (1) molecular interactions of damaged DNA and protein factors involved in the PCNA-dependent pathway; (2) mechanisms of damage recognition and b-elimination of the abasic site by pol b; (3) regulatory mechanisms of base excision repair by cell-cycle control proteins.