DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

Our laboratory investigates the link between herpesviruses and human malignancy. Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) is linked with Kaposi's sarcoma, body cavity-based lymphomas and multicentric Castleman's disease, a lymphoproliferative disorder. Our goal is to gain a better understanding of the molecular mechanisms by which KSHV exerts tumorigenic effects.

KSHV infection in tumor cells is primarily latent. In latently infected cells, KSHV persists as a multiple copy plasmid (episome). In order to persist in proliferating cells, KSHV episomes must replicate and efficiently segregate to progeny cells. The KSHV latency-associated nuclear antigen (LANA) is expressed in KSHV infected tumor cells. We have shown that LANA colocalizes with KSHV episomes on chromosomes of KSHV infected cells. In addition, LANA is necessary and sufficient to mediate persistence of episomal DNA containing a specific KSHV sequence. These data are consistent with a model in which LANA tethers KSHV episomes to chromosomes during mitosis to ensure efficient segregation of KSHV DNA to progeny cells. We are presently investigating the molecular mechanisms by which LANA serves this function.

Publications

• Kelley-Clarke B, Ballestas ME, Srinivasan V, Barbera AJ, Komatsu T, Harris TA, Kazanjian M, Kaye KM.Determination of Kaposi's sarcoma-associated herpesvirus C-terminal latency-associated nuclear antigen residues mediating chromosome association and DNA bi
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• Kelley-Clarke B, Ballestas ME, Komatsu T, Kaye KM.Kaposi's sarcoma herpesvirus C-terminal LANA concentrates at pericentromeric and peri-telomeric regions of a subset of mitotic chromosomes.Virology 2007 Jan 20;357(2):149-57.
  16979209
• Barbera AJ, Chodaparambil JV, Kelley-Clarke B, Joukov V, Walter JC, Luger K, Kaye KM.The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA.Science 2006 Feb 10;311(5762):856-61.
  16469929
• Barbera AJ, Ballestas ME, Kaye KM.The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 N terminus is essential for chromosome association, DNA replication, and episome persistence.J Virol 2004 Jan;78(1):294-301.
  14671111
• Ballestas ME, Chatis PA, Kaye KM.Efficient persistence of extrachromosomal KSHV DNA mediated by latency-associated nuclear antigen.Science 1999 Apr 23;284(5414):641-4.
  10213686