Interaction of Human Apurinic Endonuclease and DNA Polymerase β in the Base Excision Repair Pathway

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 14; pp. 7166 - 7169
• Main Authors: Richard A. O. Bennett, Wilson, David M., Wong, Donny, Demple, Bruce
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 08-07-1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Antibodies; Apes; Biochemistry; Biological Sciences; Deoxyribonuclease IV (Phage T4-Induced); Deoxyribonucleic acid; DNA; DNA Polymerase I - genetics; DNA Polymerase I - metabolism; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase; Gels; HeLa cells; Humans; Lyases - genetics; Lyases - metabolism; Nucleic acids; Oligonucleotides; Plasmids; Proteins; Saccharomyces cerevisiae; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.14.7166

Mutagenic abasic (AP) sites are generated directly by DNA-damaging agents or by DNA glycosylases acting in base excision repair. AP sites are corrected via incision by AP endonucleases, removal of deoxyribose 5-phosphate, repair synthesis, and ligation. Mammalian DNA polymerase β (Polβ ) carries out most base excision repair synthesis and also can excise deoxyribose 5-phosphate after AP endonuclease incision. Yeast two-hybrid analysis now indicates protein-protein contact between Polβ and human AP endonuclease (Ape protein). In vitro, binding of Ape protein to uncleaved AP sites loads Polβ into a ternary complex with Ape and the AP-DNA. After incision by Ape, only Polβ exhibits stable DNA binding. Kinetic experiments indicated that Ape accelerates the excision of 5′-terminal deoxyribose 5-phosphate by Polβ . Thus, the two central players of the base excision repair pathway are coordinated in sequential reactions.