The Initiation of DNA Excision-Repair

Abstract

Publisher Summary The excision-repair of Deoxyribonucleic acid (DNA) is an enzymatically mediated process by which modified bases or fragments of bases are removed from cellular DNA together with adjoining normal nucleotides. This segment of excised DNA is then resynthesized through the action of a DNA polymerase using the opposite strand as a template. The last phosphodiester bond is sealed through the action of DNA ligase. The importance of this process to human well being through the prevention of cancer was emphasized by the demonstration that in contrast to normal cells, cells of individuals with xeroderma pigmentosum (XP)—a hereditary disease—did not remove ultraviolet (UV) radiation-induced pyrimidine dimers from their nuclear DNA. The importance of the DNA repair system is emphasized by the demonstration that alkylating agents caused the onset of DNA repair synthesis when applied to human (HeLa) cells in culture. Subsequently it became evident that the DNA repair system could affect the removal of many types of modified bases in addition to pyrimidine dimmers and that DNA repair constituted a general defense mechanism against a wide variety of potentially mutagenic and/or carcinogenic DNA modifications.