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

25 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Association between the herpes simplex virus-1 DNA polymerase and uracil DNA glycosylase'. Together they form a unique fingerprint.

  • 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