Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1

AUTOR(ES)

Iftner, Thomas

FONTE

Oxford University Press

RESUMO

XRCC1 protein is required for the repair of DNA single-strand breaks and genetic stability, and is essential for viability in mammals. XRCC1 functions as a scaffold protein by interacting and modulating polypeptide components of the single-strand break repair machinery, including AP endonuclease-1, DNA ligase IIIα, poly (ADP-ribose) polymerase, DNA polymerase β and human polynucleotide kinase. We show here that the E6 protein of human papillomavirus type 1, 8 and 16 directly binds XRCC1. When tested in CHO derived XRCC1 ‘knock out’ EM9 cells, co-expression of human papillomavirus 16 E6 with human XRCC1 reduced the ability of the latter protein to correct the methyl methane sulfate sensitivity of XRCC1 mutant CHO cell line EM9. These data identify a novel link between small DNA tumour viruses and DNA repair pathways, and suggest a novel explanation for the development of genomic instability in tissue cells persistently infected with papillomaviruses.

Documentos Relacionados

• Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA repair.
• Central Role for the XRCC1 BRCT I Domain in Mammalian DNA Single-Strand Break Repair
• Physical and Functional Interaction between DNA Ligase IIIα and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair
• Genetic Requirements for the Single-Strand Annealing Pathway of Double-Strand Break Repair in Saccharomyces Cerevisiae
• Detection of protein–DNA interaction with a DNA probe: distinction between single-strand and double-strand DNA–protein interaction