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T-antigen of the human polyomavirus JC attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51.
- Source :
- Journal of Cellular Physiology; Jan2006, Vol. 206 Issue 1, p35-46, 12p, 7 Diagrams
- Publication Year :
- 2006
-
Abstract
- JC polyomavirus (JCV), which infects 90% of the human population, is detectable in human tumors. Its early protein, JCV T-antigen, transforms cells in vitro and is tumorigenic in experimental animals. Although T-antigen-mediated transformation involves genetic alterations of the affected cells, the mechanism underlying this genomic instability is not known. We show that JCV T-antigen inhibits homologous recombination DNA repair (HRR), which results in an accumulation of mutations. T-antigen does not operate directly but utilizes a cytosolic molecule, insulin receptor substrate 1 (IRS-1). Following T-antigen-mediated nuclear translocation, IRS-1 binds Rad51 at the site of damaged DNA. This T-antigen-mediated inhibition of HRR does not function in cells lacking IRS-1, and can be reproduced in the absence of T-antigen by IRS-1 with artificial nuclear localization signal. Our observations define a new mechanism by which viral protein utilizes cytosolic molecule to inhibit faithful DNA repair, and suggest how polyomaviruses could compromise stability of the genome. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
- Subjects :
- POLYOMAVIRUSES
ANTIGENS
DNA repair
TUMORS
GENETIC mutation
HUMAN genome
Subjects
Details
- Language :
- English
- ISSN :
- 00219541
- Volume :
- 206
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Journal of Cellular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 21619706
- Full Text :
- https://doi.org/10.1002/jcp.20425