Journal
JOURNAL OF GENERAL VIROLOGY
Volume 98, Issue 2, Pages 251-265Publisher
MICROBIOLOGY SOC
DOI: 10.1099/jgv.0.000681
Keywords
Epstein-Barr virus; EBV; EBNA1; regulator of chromosome condensation 1; RCC1
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Cluster de Recherche Rhone-Alpes en Infectiologie
- Ligue Contre le Cancer, Comite du Rhone
- Association pour la Recherche Contre le Cancer (ARC) [R11176CC]
- Ministere de l'Enseignement et de la Recherche Scientifique (MENRS)
- Ligue Nationale Contre le Cancer
- Medical Research Council (MRC) scholarship
Ask authors/readers for more resources
The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is a sequence-specific DNA-binding protein that plays an essential role in viral episome replication and segregation, by recruiting the cellular complex of DNA replication onto the origin (oriP) and by tethering the viral DNA onto the mitotic chromosomes. Whereas the mechanisms of viral DNA replication are well documented, those involved in tethering EBNA1 to the cellular chromatin are far from being understood. Here, we have identified regulator of chromosome condensation 1 (RCC1) as a novel cellular partner for EBNA1. RCC1 is the major nuclear guanine nucleotide exchange factor for the small GTPase Ran enzyme. RCC1, associated with chromatin, is involved in the formation of RanGTP gradients critical for nucleo-cytoplasmic transport, mitotic spindle formation and nuclear envelope reassembly following mitosis. Using several approaches, we have demonstrated a direct interaction between these two proteins and found that the EBNA1 domains responsible for EBNA1 tethering to the mitotic chromosomes are also involved in the interaction with RCC1. The use of an EBNA1 peptide array confirmed the interaction of RCC1 with these regions and also the importance of the N-terminal region of RCC1 in this interaction. Finally, using confocal microscopy and Forster resonance energy transfer analysis to follow the dynamics of interaction between the two proteins throughout the cell cycle, we have demonstrated that EBNA1 and RCC1 closely associate on the chromosomes during metaphase, suggesting an essential role for the interaction during this phase, perhaps in tethering EBNA1 to mitotic chromosomes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available