Condensin is required for chromosome arm cohesion during mitosis

Lam, Wendy; Peterson, Erica A.; Yeung, ManTek; Lavoie, Brigitte D.

doi:10.1101/gad.1468806

Cited by 66 publications

(62 citation statements)

References 64 publications

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“…The domain of chromosome V that bears URA3 has frequently been used as a reporter of genome-wide cohesion (1). Cohesin binds in and around the gene, but whether these specific complexes contribute to cohesion of the chromosomal domain is not known (15,16,27). …”

Section: Resultsmentioning

confidence: 99%

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Binding, sliding, and function of cohesin during transcriptional activation

Borrie

Campor

Joshi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The ring-shaped cohesin complex orchestrates long-range DNA interactions to mediate sister chromatid cohesion and other aspects of chromosome structure and function. In the yeast Saccharomyces cerevisiae, the complex binds discrete sites along chromosomes, including positions within and around genes. Transcriptional activity redistributes the complex to the 3′ ends of convergently oriented gene pairs. Despite the wealth of information about where cohesin binds, little is known about cohesion at individual chromosomal binding sites and how transcription affects cohesion when cohesin complexes redistribute. In this study, we generated extrachromosomal DNA circles to study cohesion in response to transcriptional induction of a model gene, URA3. Functional cohesin complexes loaded onto the locus via a poly(dA:dT) tract in the gene promoter and mediated cohesion before induction. Upon transcription, the fate of these complexes depended on whether the DNA was circular or not. When gene activation occurred before DNA circularization, cohesion was lost. When activation occurred after DNA circularization, cohesion persisted. The presence of a convergently oriented gene also prevented transcription-driven loss of functional cohesin complexes, at least in M phase-arrested cells. The results are consistent with cohesin binding chromatin in a topological embrace and with transcription mobilizing functional complexes by sliding them along DNA.T he protein complex known as cohesin organizes eukaryotic genomes into structures that segregate faithfully between dividing cells. The complex was first discovered for its role in mediating sister chromatid cohesion, but it is now known to participate in numerous aspects of chromosome biology (1, 2). Cohesin is clinically relevant because mutations in subunits of the complex or in factors that load and activate the complex lead to developmental disorders such as Cornelia de Lange syndrome, Roberts syndrome, and Warsaw breakage syndrome (3, 4).Cohesin is a ring-shaped complex composed of four subunits named Smc1, Smc3, Scc3, and Mcd1/Scc1 in budding yeast. The complex is thought to embrace DNA topologically with chromatin fibers passing through a central open channel (5-7). A substantial body of work supports a model in which cohesion arises from single cohesin complexes that embrace both sister chromatids [the double embrace model (6)]. Whether the central channel is large enough to accommodate both chromatids has recently been brought into question (8). In addition, the behavior of cohesin has not always been consistent with a double embrace by single complexes (for examples, see refs. 9-11). These situations usually involve a perturbation that causes loss of cohesion but not a loss of cohesin binding from chromatin. Such results force consideration of alternative models in which cohesin complexes embrace only one chromatid topologically and interact with other cohesin complexes or chromatin features to mediate cohesion (9,11,12).Cohesin binds densely in centromeric regions of chromos...

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Section: Resultsmentioning

confidence: 99%

“…Cohesion of the left arm of chromosome V near the endogenous URA3 locus relies on cohesin, as well as condensin (27). To determine whether these protein complexes participated in cohesion of URA3 specifically, URA3r DNA circles were monitored in strains with conditional mutations in the cohesion and condensation pathways.…”

Section: Resultsmentioning

confidence: 99%

Binding, sliding, and function of cohesin during transcriptional activation

Borrie

Campor

Joshi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Untranscribed rDNA serve as binding sites for condensin, 24 which is required for DNA damage repair and chromatid cohesion. 25 Impaired binding of condensin to untranscribed rDNA is associated with premature sister chromatids separation, before damage repair is completed. 26 Finally, UBF is an important regulator of chromatin structure at the rDNA locus; it was shown to outcompete linker Histone H1 resulting in decondensation of rDNA chromatin.…”

mentioning

confidence: 99%

Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood

Edvardson

Nicolae

Agrawal

et al. 2017

The American Journal of Human Genetics

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“…The ratio between condensin I and II and the interplay with cohesin are essential for chromosome shaping. 20 It is possible that after reformation of the nuclear envelope, a small fraction of condensin I remain in the nucleus, contributing to non-mitotic processes. 21 The role of condensin in the regulation of gene expression is elusive.…”

Section: Condensinmentioning

confidence: 99%

Structural maintenance of chromosome complexes and bone development: the beginning of a wonderful relationship?

Cohen-Zinder¹,

Karasik

Onn

2013

BoneKEy Reports

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Bone development depends on environmental, nutritional and hormonal factors. Yet, an ordered and timed activation of genes and their associated molecular pathways are central for the growth and development of healthy bones. The correct expression of genes depends on both cis-and trans-regulatory elements. Of these, the elusive role of chromatin ultrastructure is just beginning to become appreciated. Changes in the higher-order structure of chromatin are affecting the expression of genes in response to intrinsic and environmental signals. Cohesin and condensin are members of the structural maintenance of chromosome (SMC) family of protein complexes, which mediate higher-order chromatin structure by tethering distinct regions of chromatin either inter-or intra-molecularly. In recent years, SMCs had been identified for their function in the regulation of gene expression and developmental processes, whereas malfunction of cohesin or condensin has an impact on human health. However, little is known about the specific roles of SMC complexes in bone development and their possible effect on bone health. Here, we review studies that suggest an intimate link between SMCs and bone development, as well as a plausible effect, direct or indirect, on the bone health. We describe genetic syndromes associated with SMCs with distinctive bone phenotypes and identify links between SMCs and bone-related molecular pathways. Future studies of the relationship between SMCs and bone development will reveal new understandings of both the cellular and molecular roles of SMC complexes and provide new insights into the growth and developmental processes in the bone.

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Condensin is required for chromosome arm cohesion during mitosis

Cited by 66 publications

References 64 publications

Binding, sliding, and function of cohesin during transcriptional activation

Binding, sliding, and function of cohesin during transcriptional activation

Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood

Structural maintenance of chromosome complexes and bone development: the beginning of a wonderful relationship?

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