Casein kinase II-dependent phosphorylation of DNA topoisomerase II suppresses the effect of a catalytic topo II inhibitor, ICRF-193, in fission yeast.

ABSTRACT: DNA topoisomerase II (topo II) regulates the topological state of DNA and is necessary for DNA replication, transcription, and chromosome segregation. Topo II has essential functions in cell proliferation and therefore is a critical target of anticancer drugs. In this study, using Phos-tag SDS-PAGE analysis in fission yeast (Schizosaccharomyces pombe), we identified casein kinase II (Cka1/CKII)-dependent phosphorylation at the C-terminal residues Ser¹³⁶³ and Ser¹³⁶⁴ in topo II. We found that this phosphorylation decreases the inhibitory effect of an anticancer catalytic inhibitor of topo II, ICRF-193, on mitosis. Consistent with the constitutive activity of Cka1/CKII, Ser¹³⁶³ and Ser¹³⁶⁴ phosphorylation of topo II was stably maintained thr

SUBMITTER: Nakazawa N 

PROVIDER: S-EPMC6416453 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature