title: DNA-dependent cohesin cleavage by separase.
abstract: Eukaryotic genomes are organized into chromosomes. In order to maintain genomic stability during cell proliferation, a series of elaborate processes is employed to ensure that chromosomes are duplicated and segregated equally into daughter cells. Sister chromatid cohesion, a tight association of duplicated sister chromatids, allows their attachment to the opposite centrosomes. Sister chromatid cohesion depends on the cohesin complex, a proteinaceous ring that entraps the chromatids together. At the metaphase-to-anaphase transition, a protease called separase is activated and completely dissolves the cohesion by cleaving SCC1, a subunit of the cohesin complex. As one of the key executors of anaphase, separase is regulated temporally and spatially by often redundant mechanisms. A recent study revealed that chromosomal DNA is required as a cofactor for the cleavage of cohesin to occur. This DNA dependence is the underlying biochemical mechanism that allows separase to selectively cleave only the chromosome-associated cohesin. We propose that the chromosomal DNA dependent cohesin cleavage by separase is a component of a regulatory pathway that cells utilize to protect the bulk of cohesin. This intact cohesin becomes immediately available in G(1) to resume its other function-regulation of gene transcription by means of chromatin insulation.
authors.affiliation: Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Kucej
authors.forename: Hui
authors.initials: H
authors.lastname: Zou
mesh_terms: D000705:Anaphase; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D042822:Genomic Instability; D008677:Metaphase; D051379:Mice; D064247:Separase; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D010450:Endopeptidases; D064247:Separase; D000097722:Cohesins