PathwayStep2895 PathwayStep2866 Base-Excision Repair, AP Site Formation Base Excision Repair Authored: Joshi-Tope, G, 2003-07-14 15:01:00 Edited: Joshi-Tope, G, 0000-00-00 00:00:00 GENE ONTOLOGYGO:0006284 Of the three major pathways involved in the repair of nucleotide damage in DNA, base excision repair (BER) involves the greatest number of individual enzymatic activities. This is the consequence of the numerous individual glycosylases, each of which recognizes and removes a specific modified base(s) from DNA. BER is responsible for the repair of the most prevalent types of DNA lesions, alterations, which arise intracellularly as a consequence of normal mitochondrial metabolism or by oxidative free radicals resulting from ionizing radiation, lipid peroxidation or activated phagocytic cells. BER is a two-step process initiated by one of the DNA glycosylases that recognizes a specific modified base(s) and removes that base through the catalytic cleavage of the glycosylic bond, leaving an abasic site without disruption of the phosphate-sugar DNA backbone. Subsequently, abasic sites are resolved by a series of enzymes that cleave the backbone, synthesize the replacement residue(s), and ligate the DNA strand. BER may occur by either a single-nucleotide replacement pathway or a multiple-nucleotide patch replacement pathway, depending on the structure of the terminal sugar phosphate residue. The glycosylases found in human cells recognize "foreign adducts" and not standard functional modifications such as DNA methylation. Pubmed10583946 Pubmed11937636 Reactome Database ID Release 4373884 Reactome, http://www.reactome.org ReactomeREACT_1104 Resolution of Abasic Sites (AP sites)