title: PICH and BLM limit histone association with anaphase centromeric DNA threads and promote their resolution.
abstract: Centromeres nucleate the formation of kinetochores and are vital for chromosome segregation during mitosis. The SNF2 family helicase PICH (Plk1-interacting checkpoint helicase) and the BLM (the Bloom's syndrome protein) helicase decorate ultrafine histone-negative DNA threads that link the segregating sister centromeres during anaphase. The functions of PICH and BLM at these threads are not understood, however. Here, we show that PICH binds to BLM and enables BLM localization to anaphase centromeric threads. PICH- or BLM-RNAi cells fail to resolve these threads in anaphase. The fragmented threads form centromeric-chromatin-containing micronuclei in daughter cells. Anaphase threads in PICH- and BLM-RNAi cells contain histones and centromere markers. Recombinant purified PICH has nucleosome remodelling activities in vitro. We propose that PICH and BLM unravel centromeric chromatin and keep anaphase DNA threads mostly free of nucleosomes, thus allowing these threads to span long distances between rapidly segregating centromeres without breakage and providing a spatiotemporal window for their resolution.
authors: Deparment of Pharmacology, Howard Hughes Medical Institute, Dallas, TX, USA.
authors: Yuwen
authors: Y
authors: Ke
authors: Jae-Wan
authors: JW
authors: Huh
authors: Ross
authors: R
authors: Warrington
authors: Bing
authors: B
authors: Li
authors: Nan
authors: N
authors: Wu
authors: Mei
authors: M
authors: Leng
authors: Junmei
authors: J
authors: Zhang
authors: Haydn L
authors: HL
authors: Ball
authors: Bing
authors: B
authors: Li
authors: Hongtao
authors: H
authors: Yu
mesh_terms: D000705:Anaphase; D002503:Centromere / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004265:DNA Helicases / Q000502:physiology*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D048629:Micronuclei, Chromosome-Defective; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D053484:RecQ Helicases / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000502:physiology
chemical_list: D006657:Histones; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins; D004247:DNA; C097151:Bloom syndrome protein; D004265:DNA Helicases; C516980:ERCC6L protein, human; D053484:RecQ Helicases