Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening

Elbatsh, Ahmed M.O.; Haarhuis, Judith H.I.; Petela, Naomi J; Chapard, Christophe; Fish, Alexander; Celie, P.H.N.; Stadnik, M. M.; Ristić, Dejan; Wyman, Claire; Medema, René H.; Nasmyth, Kim; Rowland, Benjamin D.

doi:10.1016/j.molcel.2016.01.025

Cited by 94 publications

(154 citation statements)

References 42 publications

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“…Intriguingly, a large fraction of chromatid-bound cohesins are removed during prophase in a proteolytic-independent process that requires SA1,2/Scc3 phosphorylation [35,61]. Identifying the “gate” or subunit pair that regulates cohesin dynamics, however, is obfuscated by conflicting evidence and potentially distinct entry and exit reactions [47,62,63], reminding us that we remain in the early stages of cohesin research. Regardless, elucidating the enzymology of cohesins in different parts of the cell cycle is vital to resolve transition states through which both adaptable and stable cohesin populations are simultaneously achieved.…”

Section: Cohesin Enzymology: Is It Only About Gates?mentioning

confidence: 99%

“…Thus, mutations in Smc1 can abrogate Smc3 ATP hydrolysis and vice versa. Moreover, Smc1,3 are asymmetrically positioned within the cohesin complex, and individual ATP hydrolysis cycles appear similarly asymmetric in terms of cohesin function [18,21,62,63,66]. Thus, how ATP binding and hydrolysis and acetylation impact deposition and stability remain exciting frontiers in cohesin research.…”

Section: Cohesin Enzymology: Is It Only About Gates?mentioning

confidence: 99%

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Of Rings and Rods: Regulating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers

Skibbens

2016

PLoS Genet

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The clinical relevance of cohesin in DNA repair, tumorigenesis, and severe birth defects continues to fuel efforts in understanding cohesin structure, regulation, and enzymology. Early models depicting huge cohesin rings that entrap two DNA segments within a single lumen are fading into obscurity based on contradictory findings, but elucidating cohesin structure amid a myriad of functions remains challenging. Due in large part to integrated uses of a wide range of methodologies, recent advances are beginning to cast light into the depths that previously cloaked cohesin structure. Additional efforts similarly provide new insights into cohesin enzymology: specifically, the discoveries of ATP-dependent transitions that promote cohesin binding and release from DNA. In combination, these efforts posit a new model that cohesin exists primarily as a relatively flattened structure that entraps only a single DNA molecule and that subsequent ATP hydrolysis, acetylation, and oligomeric assembly tether together individual DNA segments.

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Section: Cohesin Enzymology: Is It Only About Gates?mentioning

confidence: 99%

Section: Cohesin Enzymology: Is It Only About Gates?mentioning

confidence: 99%

Of Rings and Rods: Regulating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers

Skibbens

2016

PLoS Genet

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“…The SMC3 expression constructs randomly integrated in the genome had an HA tag for convenient detection and were expressed from a β-actin promoter. Importantly, exogenously expressed wild-type SMC3-HA-but not an ATPasedead mutant of SMC3 (SMC3-K38I) previously shown to be required for viability (Elbatsh et al 2016)-compensated for the proliferation defects of Auxin-treated SMC3 −/3AID6Flag cells (Supplemental Fig. S3A).…”

Section: Addition Smc3mentioning

confidence: 88%

ESCO1/2's roles in chromosome structure and interphase chromatin organization

et al. 2017

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ESCO1/2 acetyltransferases mediating SMC3 acetylation and sister chromatid cohesion (SCC) are differentially required for genome integrity and development. Here we established chicken DT40 cell lines with mutations in ESCO1/2, SMC3 acetylation, and the cohesin remover WAPL. Both ESCO1 and ESCO2 promoted SCC, while ESCO2 was additionally and specifically required for proliferation and centromere integrity. ESCO1 overexpression fully suppressed the slow proliferation and centromeric separation phenotypes of esco2 cells but only partly suppressed its chromosome arm SCC defects. Concomitant inactivation of ESCO1 and ESCO2 caused lethality owing to compromised mitotic chromosome segregation. Neither wapl nor acetyl-mimicking smc3-QQ mutations rescued esco1 esco2 lethality. Notably, esco1 esco2 wapl conditional mutants showed very severe proliferation defects associated with catastrophic mitoses and also abnormal interphase chromatin organization patterns. The results indicate that cohesion establishment by vertebrate ESCO1/2 is linked to interphase chromatin architecture formation, a newly identified function of cohesin acetyltransferases that is both fundamentally and medically relevant.

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“…Another possibility is that the actual agent of MukB ATPase activity is a conglomerate of MukB dimers associated head-to-head and that the MukF dimer need only bind to one end of the chain to trigger ATP hydrolysis throughout. A recent study of DNA release by the yeast cohesin showed that asym- metric ATP hydrolysis by the head domains of Smc1 and Smc3 was involved (32). Perhaps the head domains in a MukB dimer are also non-equivalent.…”

Section: Topological Alteration Of the Dna Observed In The Reactionsmentioning

confidence: 99%

MukB-mediated Catenation of DNA Is ATP and MukEF Independent

Bahng

Hayama

Marians

2016

Journal of Biological Chemistry

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Edited by Patrick SungProperly condensed chromosomes are necessary for accurate segregation of the sisters after DNA replication. The Escherichia coli condesin is MukB, a structural maintenance of chromosomes (SMC)-like protein, which forms a complex with MukE and the kleisin MukF. MukB is known to be able to mediate knotting of a DNA ring, an intramolecular reaction. In our investigations of how MukB condenses DNA we discovered that it can also mediate catenation of two DNA rings, an intermolecular reaction. This activity of MukB requires DNA binding by the head domains of the protein but does not require either ATP or its partner proteins MukE or MukF. The ability of MukB to mediate DNA catenation underscores its potential for bringing distal regions of a chromosome together.The Escherichia coli chromosome is condensed about 1000-fold to fit into the nucleoid of the bacterium. A number of factors contribute to this extreme DNA condensation, among them are: DNA supercoiling, the binding of various nucleoid associated proteins like HU, Fis, and H-NS, and the binding of the structural maintenance of chromosomes (SMC) 3 -like condensin MukBEF (1, 2). SMC proteins act to manage the shape and behavior of chromosomes in both prokaryotes and eukaryotes (3). These proteins dimerize at a hinge region that is flanked by long coiled-coil regions that can be 40 -50 nm in length and that end in head domains that bind and hydrolyze ATP, as well as the bridging kleisin protein (MukF for the E. coli condensin (4)). The kleisin is then itself bound by another protein (MukE for the E. coli condensin (4)). There are three versions of the eukaryotic SMC proteins: the condensin, required for packaging of the chromosomes and comprised of SMC2 and SMC4; the cohesin, required for holding sister chromosomes together during mitosis and comprised of SMC1 and SMC3; and the SMC5-SMC6 complex, required for various aspects of DNA repair (3).It is generally acknowledged that the eukaryotic condensin and cohesin trap DNA topologically in the protein triangle formed by the SMC proteins and the kleisin (5, 6), although an alternative model for DNA binding for the eukaryotic cohesin exists (7). Recent reports suggest that the Bacillus subtilis SMC protein (8) and MukB (9) also trap chromosomes topologically. MukB binds linear and circular DNA in vitro and can induce negative supercoils and knots in relaxed circular DNA in the presence of a topoisomerase (10). Binding of MukB to chromosomal DNA in vivo requires ATP and MukEF (11, 12), although MukB DNA binding in vitro does not (10, 13).We (14) and the Burger and Oakley (15) labs have shown that the MukB hinge region interacts with the C-terminal ␤-propeller region of the ParC subunit of the cellular decatenase topoisomerase IV (Topo IV). We have reported (16) that this interaction stimulates the intramolecular activities of Topo IV, negative supercoil relaxation and knotting, but not the intermolecular activities of Topo IV, catenation/decatenation of DNA rings; whereas Berger, Oakley and colleag...

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Cohesin Releases DNA through Asymmetric ATPase-Driven Ring Opening

Cited by 94 publications

References 42 publications

Of Rings and Rods: Regulating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers

Of Rings and Rods: Regulating Cohesin Entrapment of DNA to Generate Intra- and Intermolecular Tethers

ESCO1/2's roles in chromosome structure and interphase chromatin organization

MukB-mediated Catenation of DNA Is ATP and MukEF Independent

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