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Topoisomerase IIIα is required for normal proliferation and telomere stability in alternative lengthening of telomeres
Author(s) -
TemimeSmaali Nassima,
Guittat Lionel,
Wenner Thomas,
Bayart Emilie,
Douarre Céline,
Gomez Dennis,
GiraudPanis MarieJosèphe,
LondonoVallejo Arturo,
Gilson Eric,
AmorGuéret Mounira,
Riou JeanFrançois
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.74
Subject(s) - telomere , biology , telomerase , telomere binding protein , microbiology and biotechnology , topoisomerase , telomerase reverse transcriptase , chromatin , immunoprecipitation , helicase , chromatin immunoprecipitation , dna , rna , cell culture , dna binding protein , genetics , gene expression , gene , transcription factor , promoter
Topoisomerase (Topo) IIIα associates with BLM helicase, which is proposed to be important in the alternative lengthening of telomeres (ALT) pathway that allows telomere recombination in the absence of telomerase. Here, we show that human Topo IIIα colocalizes with telomeric proteins at ALT‐associated promyelocytic bodies from ALT cells. In these cells, Topo IIIα immunoprecipitated with telomere binding protein (TRF) 2 and BLM and was shown to be associated with telomeric DNA by chromatin immunoprecipitation, suggesting that these proteins form a complex at telomere sequences. Topo IIIα depletion by small interfering RNA reduced ALT cell survival, but did not affect telomerase‐positive cell lines. Moreover, repression of Topo IIIα expression in ALT cells reduced the levels of TRF2 and BLM proteins, provoked a strong increase in the formation of anaphase bridges, induced the degradation of the G‐overhang signal, and resulted in the appearance of DNA damage at telomeres. In contrast, telomere maintenance and TRF2 levels were unaffected in telomerase‐positive cells. We conclude that Topo IIIα is an important telomere‐associated factor, essential for telomere maintenance and chromosome stability in ALT cells, and speculate on its potential mechanistic function.