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Association between the Herpes Simplex Virus-1 DNA Polymerase and Uracil DNA Glycosylase
- Source :
- Journal of Biological Chemistry. 285:27664-27672
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
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 IIIalpha-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.
- Subjects :
- DNA Replication
DNA Repair
DNA polymerase
DNA polymerase II
DNA-Directed DNA Polymerase
Genome, Viral
Herpesvirus 1, Human
DNA and Chromosomes
Virus Replication
Biochemistry
Multienzyme Complexes
Catalytic Domain
AP site
Uracil-DNA Glycosidase
Molecular Biology
Replication protein A
DNA clamp
biology
Cell Biology
Molecular biology
Protein Transport
DNA glycosylase
Uracil-DNA glycosylase
DNA, Viral
biology.protein
Protein Binding
Nucleotide excision repair
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 285
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....6d5356879a46333165e5d5b9b5e38fdc