RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression.
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 IIα with RECQL5, one of five mammalian RecQ helicases, during DNA replication. Direct interaction of RECQL5 with Topoisomerase IIα stimulates the decatenation activity of Topoisomerase IIα. Consistent with these observations, RECQL5 co-localizes with Topoisomerase IIα 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.
Laboratory of Molecular Gerontology, Biomedical Research Center, 251 Bayview Boulevard, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Mahesh
M
Ramamoorthy
Takashi
T
Tadokoro
Ivana
I
Rybanska
Avik K
AK
Ghosh
Robert
R
Wersto
Alfred
A
May
Tomasz
T
Kulikowicz
Peter
P
Sykora
Deborah L
DL
Croteau
Vilhelm A
VA
Bohr
D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D049109:Cell Proliferation; D002869:Chromosome Aberrations; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D043864:DNA, Catenated / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D008677:Metaphase / Q000235:genetics; D053484:RecQ Helicases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071657:Werner Syndrome Helicase
D000951:Antigens, Neoplasm; D043864:DNA, Catenated; D004268:DNA-Binding Proteins; C506732:RECQL5 protein, human; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D004250:DNA Topoisomerases, Type II