Kaposi's Sarcoma-Associated Herpesvirus Deregulates Host Cellular Replication during Lytic Reactivation by Disrupting the MCM Complex through ORF59

Journal of Virology
Roxanne C StrahanSubhash C Verma

Abstract

Minichromosome maintenance proteins (MCMs) play an important role in DNA replication by binding to the origins as helicase and recruiting polymerases for DNA synthesis. During the S phase, MCM complex is loaded to limit DNA replication once per cell cycle. We identified MCMs as ORF59 binding partners in our protein pulldown assays, which led us to hypothesize that this interaction influences DNA replication. ORF59's interactions with MCMs were confirmed in both endogenous and overexpression systems, which showed its association with MCM3, MCM4, MCM5, and MCM6. Interestingly, MCM6 interacted with both the N- and C-terminal domains of ORF59, and its depletion in BCBL-1 and BC3 cells led to an increase in viral genome copies, viral late gene transcripts, and virion production compared to the control cells following reactivation. MCMs perform their function by loading onto the replication competent DNA, and one means of regulating chromatin loading/unloading, in addition to enzymatic activity of the MCM complex, is by posttranslational modifications, including phosphorylation of these factors. Interestingly, a hypophosphorylated form of MCM3, which is associated with reduced loading onto the chromatin, was detected during lytic rea...Continue Reading

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Citations

Jun 6, 2020·The Journal of General Virology·Robert HollingworthRoger J Grand
Feb 21, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Tian ZengJuan Zou
Mar 30, 2021·Virus Research·Beata Cohan, Lori Frappier

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