RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression.
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Ramamoorthy M, Tadokoro T, Rybanska I, Ghosh AK, Wersto R, May A, Kulikowicz T, Sykora P, Croteau DL, Bohr VA
RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression.
Nucleic Acids Res. 2012 Feb;40(4):1621-35. doi: 10.1093/nar/gkr844. Epub 2011 Oct 19.
- PubMed ID
- 22013166 [ View in PubMed]
- Abstract
DNA decatenation mediated by Topoisomerase II is required to separate the interlinked sister chromatids post-replication. SGS1, a yeast homolog of the human RecQ family of helicases interacts with Topoisomerase II and plays a role in chromosome segregation, but this functional interaction has yet to be identified in higher organisms. Here, we report a physical and functional interaction of Topoisomerase IIalpha with RECQL5, one of five mammalian RecQ helicases, during DNA replication. Direct interaction of RECQL5 with Topoisomerase IIalpha stimulates the decatenation activity of Topoisomerase IIalpha. Consistent with these observations, RECQL5 co-localizes with Topoisomerase IIalpha during S-phase of the cell cycle. Moreover, cells with stable depletions of RECQL5 display a slow proliferation rate, a G2/M cell cycle arrest and late S-phase cycling defects. Metaphase spreads generated from RECQL5-depleted cells exhibit undercondensed and entangled chromosomes. Further, RECQL5-depleted cells activate a G2/M checkpoint and undergo apoptosis. These phenotypes are similar to those observed when Topoisomerase II catalytic activity is inhibited. These results reveal an important role for RECQL5 in the maintenance of genomic stability and a new insight into the decatenation process.