TOPOISOMERASE IIa PREVENTS ULTRAFINE ANAPHASE BRIDGES BY TWO MECHANISMS

ABSTRACT: Topoisomerase IIa (Topo IIa), a well-conserved double-stranded DNA (dsDNA)-specific decatenase, processes dsDNA catenanes resulting from DNA replication during mitosis. Topo IIa defects lead to an accumulation of ultrafine anaphase bridges (UFBs), a type of chromosome non-disjunction. Topo IIa has been reported to resolve DNA anaphase threads, possibly accounting for the increase in UFB frequency upon Topo IIa inhibition. We hypothesized that the excess UFBs might also result, at least in part, from an impairment of the prevention of UFB formation by Topo IIa. We found that Topo IIa inhibition promotes UFB formation without affecting the global disappearance of UFBs during mitosis, but leads to an aberrant UFB resolution generating DNA damage within the next G1. Moreover, we demonstrated t

SUBMITTER: Gemble Simon 

PROVIDER: S-BSST378 | biostudies-other |

REPOSITORIES: biostudies-other