title: The replicative DNA polymerase of herpes simplex virus 1 exhibits apurinic/apyrimidinic and 5'-deoxyribose phosphate lyase activities.
abstract: Base excision repair (BER) is essential for maintaining genome stability both to counter the accumulation of unusual bases and to protect from base loss in the DNA. Herpes simplex virus 1 (HSV-1) is a large dsDNA virus that encodes its own DNA replication machinery, including enzymes involved in nucleotide metabolism. We report on a replicative family B and a herpesvirus-encoded DNA Pol that possesses DNA lyase activity. We have discovered that the catalytic subunit of the HSV-1 DNA polymerase (Pol) (UL30) exhibits apurinic/apyrimidinic (AP) and 5'-deoxyribose phosphate (dRP) lyase activities. These activities are integral to BER and lead to DNA cleavage on the 3' side of abasic sites and 5'-dRP residues that remain after cleavage by 5'-AP endonuclease. The UL30-catalyzed reaction occurs independently of divalent cation and proceeds via a Schiff base intermediate, indicating that it occurs via a lyase mechanism. Partial proteolysis of the Schiff base shows that the DNA lyase activity resides in the Pol domain of UL30. These observations together with the presence of a virus-encoded uracil DNA glycosylase indicates that HSV-1 has the capacity to perform critical steps in BER. These findings have implications on the role of BER in viral genome maintenance during lytic replication and reactivation from latency.
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine, 425 North 5th Street, Phoenix, AZ 85004-2157, USA.
authors.forename: Federica
authors.initials: F
authors.lastname: Bogani
authors.forename: Paul E
authors.initials: PE
authors.lastname: Boehmer
mesh_terms: D000818:Animals; D002460:Cell Line; D004261:DNA Replication / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics*; D007700:Kinetics; D019761:Phosphorus-Oxygen Lyases / Q000302:isolation & purification / Q000378:metabolism*; D011119:Polynucleotides / Q000378:metabolism*; D012267:Ribosemonophosphates / Q000378:metabolism; D018411:Spodoptera; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C502791:5'-deoxyribose-5-phosphate; D004279:DNA, Viral; D011119:Polynucleotides; D012267:Ribosemonophosphates; D014764:Viral Proteins; C423906:5'-deoxyribose phosphate lyase; D004259:DNA-Directed DNA Polymerase; D005090:Exodeoxyribonucleases; C043417:DNA polymerase, Simplexvirus; D019761:Phosphorus-Oxygen Lyases