title: Molecular mechanism of PCNA-dependent base excision repair.
abstract: In higher eukaryotes, base excision repair can proceed by two alternative pathways: a DNA polymerase beta-dependent pathway and a proliferating cell nuclear antigen (PCNA)-dependent pathway. Recently, we have reconstituted the PCNA-dependent AP site repair reaction with six purified human proteins: AP endonuclease, replication factor C (RFC), PCNA, flap endonuclease 1 (FEN1), DNA polymerase delta (pol delta), and DNA ligase I. In this reconstituted system, the number of nucleotides replaced during the repair reaction (patch size) was predominantly two nucleotides. PCNA can directly interact with RFC, pol delta, FEN1 and DNA ligase I. These interactions are partly through a consensus motif, QXX(I/L/M)XX(F/H)(F/Y), found in each of the four proteins. PCNA functions as a molecular adaptor for recruiting these factors to the site of DNA repair. Two DNA-N-glycosylases among those so far cloned from human, UNG2 and MYH, are found to have the same PCNA-binding motif. Major substrates of these enzymes, a uracil opposite an adenine for UNG2 and an adenine opposite an 8-oxoguanine for MYH, are formed during DNA replication. Therefore, UNG2 and MYH may serve for replication-coupled base excision repair through the direct interaction with PCNA in the replication machinery.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001080:Apurinic Acid / Q000378:metabolism; D001665:Binding Sites; D019757:Carbon-Oxygen Lyases / Q000502:physiology; D002474:Cell-Free System; D016384:Consensus Sequence; D045647:DNA Glycosylases; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000502:physiology; D004258:DNA Polymerase III / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D004261:DNA Replication; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000502:physiology; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004706:Endodeoxyribonucleases / Q000502:physiology; D045585:Flap Endonucleases; D006801:Humans; D046911:Macromolecular Substances; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000502:physiology*; D051818:Replication Protein C; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D051981:Uracil-DNA Glycosidase
chemical_list: D004268:DNA-Binding Proteins; C000607892:LIG1 protein, human; D046911:Macromolecular Substances; D018809:Proliferating Cell Nuclear Antigen; D001080:Apurinic Acid; D004258:DNA Polymerase III; D004706:Endodeoxyribonucleases; D045585:Flap Endonucleases; C468317:FEN1 protein, human; D043223:Deoxyribonuclease IV (Phage T4-Induced); D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; C061738:mutY adenine glycosylase; D051818:Replication Protein C; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases; D000072481:DNA Ligase ATP