Bloom’s syndrome and PICH helicases cooperate with topoisomerase IIα in centromere disjunction before anaphase.
PLoS ONE. 2012-04-26; 7(4): e33905
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1. PLoS One. 2012;7(4):e33905. doi: 10.1371/journal.pone.0033905. Epub 2012 Apr 26.
Bloom’s syndrome and PICH helicases cooperate with topoisomerase IIα in
centromere disjunction before anaphase.
Rouzeau S(1), Cordelières FP, Buhagiar-Labarchède G, Hurbain I, Onclercq-Delic R,
Gemble S, Magnaghi-Jaulin L, Jaulin C, Amor-Guéret M.
(1)Institut Curie, Centre de Recherche, Centre Universitaire, Bât, Orsay, France.
Centromeres are specialized chromosome domains that control chromosome
segregation during mitosis, but little is known about the mechanisms underlying
the maintenance of their integrity. Centromeric ultrafine anaphase bridges are
physiological DNA structures thought to contain unresolved DNA catenations
between the centromeres separating during anaphase. BLM and PICH helicases
colocalize at these ultrafine anaphase bridges and promote their resolution. As
PICH is detectable at centromeres from prometaphase onwards, we hypothesized that
BLM might also be located at centromeres and that the two proteins might
cooperate to resolve DNA catenations before the onset of anaphase. Using
immunofluorescence analyses, we demonstrated the recruitment of BLM to
centromeres from G2 phase to mitosis. With a combination of fluorescence in situ
hybridization, electron microscopy, RNA interference, chromosome spreads and
chromatin immunoprecipitation, we showed that both BLM-deficient and
PICH-deficient prometaphase cells displayed changes in centromere structure.
These cells also had a higher frequency of centromeric non disjunction in the
absence of cohesin, suggesting the persistence of catenations. Both proteins were
required for the correct recruitment to the centromere of active topoisomerase
IIα, an enzyme specialized in the catenation/decatenation process. These
observations reveal the existence of a functional relationship between BLM, PICH
and topoisomerase IIα in the centromere decatenation process. They indicate that
the higher frequency of centromeric ultrafine anaphase bridges in BLM-deficient
cells and in cells treated with topoisomerase IIα inhibitors is probably due not
only to unresolved physiological ultrafine anaphase bridges, but also to newly
formed ultrafine anaphase bridges. We suggest that BLM and PICH cooperate in
rendering centromeric catenates accessible to topoisomerase IIα, thereby
facilitating correct centromere disjunction and preventing the formation of
supernumerary centromeric ultrafine anaphase bridges.
PMID: 22563370 [Indexed for MEDLINE]