How a Tumor Virus Destabilizes the Genome (image)

PLOS

Caption

Bub1-mediated H2A phosphorylation at residue T120 recruits Sgo1 to centromeres to protect cohesin and Bub1-mediated Cdc20 phosphorylation inhibits the activity of Separase. Cells will be arrested at mitosis until all kinetochores are attached to microtubules. KSHV encoded LANA disrupts the interactions between Bub1, Cdc20 and H2A, inhibiting Cdc20 and H2A phosphorylation. Failure of Sgo1 recruitment because of lacking H2AT120 phosphorylation results in loss of protection for cohesin. Inhibition of Cdc20 phosphorylation leads to aberrant activation of Separase and destruction of cohesin. This will lead to premature mitotic exit and induce chromosomal instabilities.

Credit

Lang F, Sun Z, Pei Y, Singh RK, Jha HC, Robertson ES (2018)

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