title: DNA ligase I selectively affects DNA synthesis by DNA polymerases delta and epsilon suggesting differential functions in DNA replication and repair.
abstract: The joining of single-stranded breaks in double-stranded DNA is an essential step in many important processes such as DNA replication, DNA repair, and genetic recombination. Several data implicate a role for DNA ligase I in DNA replication, probably coordinated by the action of other enzymes and proteins. Since both DNA polymerases delta and epsilon show multiple functions in different DNA transactions, we investigated the effect of DNA ligase I on various DNA synthesis events catalyzed by these two essential DNA polymerases. DNA ligase I inhibited replication factor C-independent DNA synthesis by polymerase delta. Our results suggest that the inhibition may be due to DNA ligase I interaction with proliferating cell nuclear antigen (PCNA) and not to a direct interaction with the DNA polymerase delta itself. Strand displacement activity by DNA polymerase delta was also affected by DNA ligase I. The DNA polymerase delta holoenzyme (composed of DNA polymerase delta, PCNA, and replication factor C) was inhibited in the same way as the DNA polymerase delta core, strengthening the hypothesis of a PCNA interaction. Contrary to DNA polymerase delta, DNA synthesis by DNA polymerase epsilon was stimulated by DNA ligase I in a PCNA-dependent manner. We conclude that DNA ligase I displays different influences on the two multipotent DNA polymerases delta and epsilon through PCNA. This might be of importance in the selective involvement in DNA transactions such as DNA replication and various mechanisms of DNA repair.
authors.affiliation: Institute of Veterinary Biochemistry, University of Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Mossi
authors.forename: E
authors.initials: E
authors.lastname: Ferrari
authors.forename: U
authors.initials: U
authors.lastname: Hübscher
mesh_terms: D004247:DNA / Q000096:biosynthesis*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000502:physiology*; D004257:DNA Polymerase II / Q000378:metabolism*; D004258:DNA Polymerase III / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D018398:Homeodomain Proteins; D006801:Humans; D007700:Kinetics; D015778:Minor Histocompatibility Antigens; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011067:Poly dA-dT / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins
chemical_list: C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C000607892:LIG1 protein, human; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D009838:Oligodeoxyribonucleotides; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C016069:poly (dA).oligo((d)T); D011067:Poly dA-dT; D004247:DNA; D004257:DNA Polymerase II; D004258:DNA Polymerase III; D051818:Replication Protein C; D011088:DNA Ligases; D000072481:DNA Ligase ATP