DNA Polymerase β and Mammalian Base Excision Repair
This extract was created in the absence of an abstract.
Excerpt
Proficient DNA repair systems are critical to maintaining the stability of the genome in organisms throughoutnature. Many types of endogenously and exogenously induced base damage, including alkylation, oxidation, anddeamination, result in the formation of abasic sites andsingle-stranded nicks in DNA. These lesions may occureither spontaneously or as intermediates in repair. The resulting nicks and abasic sites are repaired mainly by thebase excision repair (BER) pathway to prevent the accumulation of lesions. In mammalian BER, the abasic site isrecognized by apurinic/apyrimidinic (AP) endonuclease,which incises the damaged strand, leaving a single nucleotide gap with 3′-OH and 5′-deoxyribose phosphate(dRP) groups at the margins. The gap is then processed byDNA polymerase β (pol-β) via DNA synthesis and dRPlyase steps to create nicked DNA that will be ligated byDNA ligase I or III. Thus, pol-β possesses both nucleotidyl transferase activity necessary to fill the singlenucleotide gap and lyase activity required to remove thedRP flap. Processing of the single-stranded nick in DNAafter radiation-induced or reactive oxygen species-induced strand cleavage is also mediated by pol-β-dependent single-nucleotide gap-filling...
