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- Title
The EBNA- 3 gene family proteins disrupt the G2/M checkpoint.
- Authors
Buck, Marion; Flanagan, James; Krauer, Kenia G.; Sculley, Tom B.; Burgess, Andrew; Gabrielli, Brian
- Abstract
The Epstein-Barr nuclear antigens (EBNA), EBNA-3, -4 and -6, have previously been shown to act as transcriptional regulators, however, this study identifies another function for these proteins, disruption of the G2/M checkpoint. Lymphoblastoid cell lines (LCLs) treated with a G2/M initiating drug azelaic bishydroxamine (ABHA) did not show a G2/M checkpoint response, but rather they display an increase in cell death, a characteristic of sensitivity to the cytotoxic effects of the drug. Cell cycle analysis demonstrated that the individual expression of EBNA-3, -4 or -6 are capable of disrupting the G2/M checkpoint response induced by ABHA resulting in increased toxicity, whereas EBNA-2, and -5 were not. EBNA-3 gene family protein expression also disrupted the G2/M checkpoint initiated in response to the genotoxin etoposide and the S?phase inhibitor hydroxyurea. The G2 arrest in response to these drugs were sensitive to caffeine, suggesting that ATM/ATR signalling in these checkpoint responses may be blocked by the EBNA-3 family proteins. The function of EBNA-3, -4 and -6 proteins appears to be more complex than anticipated and these data suggest a role for these proteins in disrupting the host cell cycle machinery.Oncogene (2004) 23, 1342-1353 doi:10.1038/sj.onc.1207253 Published online 29 December 2003
- Publication
Oncogene, 2004, Vol 23, Issue 7, p1342
- ISSN
0950-9232
- Publication type
Academic Journal
- DOI
10.1038/sj.onc.1207253