Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase

Federica Bogani, Ilsa Corredeira, Virneliz Fernandez, Ulrike Sattler, Wiriya Rutvisuttinunt, Martine Defais, Paul E Boehmer

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Herpes simplex virus-1 (HSV-1) is a large dsDNA virus that encodes its own DNA replication machinery and other enzymes involved in DNA transactions. We recently reported that the HSV-1 DNA polymerase catalytic subunit (UL30) exhibits apurinic/apyrimidinic and 5′-deoxyribose phosphate lyase activities. Moreover, UL30, in conjunction with the viral uracil DNA glycosylase (UL2), cellular apurinic/apyrimidinic endonuclease, and DNA ligase IIIα-XRCC1, performs uracil-initiated base excision repair. Base excision repair is required to maintain genome stability as a means to counter the accumulation of unusual bases and to protect from the loss of DNA bases. Here we show that the HSV-1 UL2 associates with the viral replisome. We identified UL2 as a protein that co-purifies with the DNA polymerase through numerous chromatographic steps, an interaction that was verified by co- immunoprecipitation and direct binding studies. The interaction between UL2 and the DNA polymerase is mediated through the UL30 subunit. Moreover, UL2 co-localizes with UL30 to nuclear viral prereplicative sites. The functional consequence of this interaction is that replication of uracil-containing templates stalls at positions -1 and -2 relative to the template uracil because of the fact that these are converted into non-instructional abasic sites. These findings support the existence of a viral repair complex that may be capable of replication-coupled base excision repair and further highlight the role of DNA repair in the maintenance of the HSV-1 genome.

Original languageEnglish (US)
Pages (from-to)27664-27672
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number36
DOIs
StatePublished - Sep 3 2010

Fingerprint

Uracil-DNA Glycosidase
Human Herpesvirus 1
DNA-Directed DNA Polymerase
Viruses
DNA Repair
Uracil
Repair
DNA
DNA-(Apurinic or Apyrimidinic Site) Lyase
Genes
Genomic Instability
Viral DNA
DNA Ligases
DNA Replication
Immunoprecipitation
Catalytic Domain
Maintenance
Machinery
Genome
Simplexvirus DNA polymerase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Bogani, F., Corredeira, I., Fernandez, V., Sattler, U., Rutvisuttinunt, W., Defais, M., & Boehmer, P. E. (2010). Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase. Journal of Biological Chemistry, 285(36), 27664-27672. https://doi.org/10.1074/jbc.M110.131235

Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase. / Bogani, Federica; Corredeira, Ilsa; Fernandez, Virneliz; Sattler, Ulrike; Rutvisuttinunt, Wiriya; Defais, Martine; Boehmer, Paul E.

In: Journal of Biological Chemistry, Vol. 285, No. 36, 03.09.2010, p. 27664-27672.

Research output: Contribution to journalArticle

Bogani, F, Corredeira, I, Fernandez, V, Sattler, U, Rutvisuttinunt, W, Defais, M & Boehmer, PE 2010, 'Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase', Journal of Biological Chemistry, vol. 285, no. 36, pp. 27664-27672. https://doi.org/10.1074/jbc.M110.131235
Bogani F, Corredeira I, Fernandez V, Sattler U, Rutvisuttinunt W, Defais M et al. Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase. Journal of Biological Chemistry. 2010 Sep 3;285(36):27664-27672. https://doi.org/10.1074/jbc.M110.131235
Bogani, Federica ; Corredeira, Ilsa ; Fernandez, Virneliz ; Sattler, Ulrike ; Rutvisuttinunt, Wiriya ; Defais, Martine ; Boehmer, Paul E. / Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 36. pp. 27664-27672.
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