Mitotic chromosome interactions of Epstein-Barr nuclear antigen 1 (EBNA1) and human EBNA1-binding protein 2 (EBP2)

Abstract

by tethering the episomes to the cellular chromosomes in mitosis. A host nucleolar protein, EBNA1-binding protein 2 (EBP2), has been shown to be important for interactions between EBNA1 and chromosomes in metaphase and to associate with metaphase chromosomes. Here, we examine the timing of the chromosome associations of EBNA1 and EBP2 through mitosis and the regions of EBNA1 that mediate the chromosome interactions at each stage of mitosis. We show that EBP2 is localized to the nucleolus until late prophase, after which it relocalizes to the chromosome periphery, where it remains throughout telophase. EBNA1 is associated with chromosomes early in prophase through to telophase and partially colocalizes with chromosomal EBP2 in metaphase through to telophase. Using EBNA1 deletion mutants, the chromosome association of EBNA1 at each stage of mitosis was found to be mediated mainly by a central glycinearginine region, and to a lesser degree by N-terminal sequences. These sequence requirements for chromosome interaction mirrored those for EBP2 binding. Our results suggest that interactions between EBNA1 and chromosomes involve at least two stages, and that the contribution of EBP2 to these interactions occurs in the second half of mitosis.

Intracellular partitioning of cell organelles and extraneous nanoparticles during mitosis

“…EBNA1 binds directly to viral DNA via its C-terminal domain and tethers the EBV genome to chromatin through its N-terminal domain, initially by direct interactions via its AT hooks, or afterwards through association with the nucleolar EBNA1 binding protein 2 (EBP2). The latter is a part of the perichromosomal layer and the binding with EBNA1 may be required to stabilize the EBNA1-chromosome interaction [149].…”

“…Murine leukemia virus (MuLV) (p12) [133,134] Human immunodeficiency virus (HIV) (LEDGF/p75) [141] Avian sarcoma virus (ASV) (IN) [132] Foamy virus (FV) (Gag) [143,144] Epstein Barr virus (EBV) EBNA1 [147][148][149] Kaposi sarcoma-associated herpesvirus (KSHV) LANA [151,152,154] Bovine (BPV) and human papillomavirus (HPV) E2 [155][156][157][158] Simian vacuolating virus 40 (SV40) unknown [161,162] …”

Modelling the structure of full-length Epstein–Barr virus nuclear antigen 1

“…LR2 or GR2 (residues 327-377) is also a Gly and Arg repeating unit. A host nucleolar protein, EBP2, associates with EBNA1 at GR1 and GR2, which might facilitate loading of EBNA1 onto mitotic chromosomes (25,26).…”

Potential Therapeutic Molecular Targets for Nasopharyngeal Carcinoma

“…Stable complex formation between EBNA1 and the nucleosome assembly proteins, NAP1 and TAF-I, can affect cellular DNA replication (309). The EBNA1 portion of the EBNA1-binding protein 2 complex was shown to promote its interaction with mitotic chromosomes (218). A recent study has demonstrated that high-level expression of the EBNA1 protein in NPC cells interferes with mitotic segregation (275).…”