Base excision repair (BER) is a frontline repair system that is responsible for 
maintaining genome integrity and thus preventing premature aging, cancer and 
many other human diseases by repairing thousands of DNA lesions and strand 
breaks continuously caused by endogenous and exogenous mutagens. This 
fundamental and essential function of BER not only necessitates tight control of 
the continuous availability of basic components for fast and accurate repair, 
but also requires temporal and spatial coordination of BER and cell cycle 
progression to prevent replication of damaged DNA. The major goal of this review 
is to critically examine controversial and newly emerging questions about 
mammalian BER pathways, mechanisms regulating BER capacity, BER responses to DNA 
damage and their links to checkpoint control of DNA replication.