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Regulation of sister chromatid cohesion in mammalian cells
Author(s) -
Peters JanMichael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a95-a
Subject(s) - cohesin , separase , establishment of sister chromatid cohesion , anaphase , microbiology and biotechnology , chromosome segregation , sister chromatids , prophase , mitosis , biology , chromatin , centromere , metaphase , chemistry , genetics , meiosis , cell cycle , chromosome , cell , dna , gene
Sister chromatids are connected by cohesin complexes. This cohesion is essential to allow the bipolar attachment of chromosomes to the spindle, whereas the subsequent removal of cohesin from chromosomes is required for anaphase. In vertebrates, the bulk of cohesin is removed from chromosome arms already in prophase by a mechanism that depends on the mitotic kinases Plk1 and Aurora B, and on the protein complex condensin I. Cohesin at centromeres is protected from this “prophase pathway” by a protein called Sgo1. In metaphase, the protease separase is activated, cleaves the Scc1 subunit of centromeric cohesin and thereby initiates anaphase. To identify additional proteins that might control the association of cohesin with chromatin we have purified human cohesin and analyzed associated proteins by mass spectrometry. We have identified an ortholog of the Drosophila protein Wapl (wings‐apart like) that has been implicated in heterochromatin formation and chromosome segregation. Human Wapl is specifically associated with cohesin throughout the cell cycle and, like cohesin, is associated with chromatin from telophase until prophase of the next mitosis. Depletion of Wapl blocks cohesin dissociation from chromosomes during the early stages of mitosis and prevents the resolution of sister chromatids until anaphase, which occurs after a delay. FRAP experiments revealed that Wapl depletion also increases the residence time of cohesin on chromatin in interphase. Based on our data we propose that Wapl is part of a molecular device that is required to unlock cohesin from a particular state in which it is stably bound to chromatin.