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Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE235560 | GEO | 2024/01/30

REPOSITORIES: GEO

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Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [RNA-seq]

Project description:The Structural Maintenance of Chromosome (SMC) protein complexes cohesin, condensin and the Smc5/6 complex (Smc5/6) are essential for chromosome function. At the molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates chromosome loops in interphase, and condensin compacts mitotic chromosomes. However, the role of Smc5/6’s recently discovered DNA loop extrusion activity is unknown. Here, we uncover that Smc5/6 controls the spatial organization of supercoiled chromosomal regions. The results show that Smc5/6 associates with transcription-induced positively supercoiled chromosomal DNA at cohesin-dependent chromosome loop boundaries. Mechanistically, single-molecule imaging reveals that dimers of Smc5/6 specifically recognize the tip of positively supercoiled DNA plectonemes, and efficiently initiates loop extrusion to gather the supercoiled DNA into a large plectonemic loop. Finally, Hi-C analysis shows that Smc5/6 links chromosomal regions containing transcription-induced positive supercoiling in cis. Altogether, our findings indicate that Smc5/6 controls the three-dimensional organization of chromosomes by recognizing and initiating loop extrusion on positively supercoiled DNA.

2024-01-30 | GSE235559 | GEO

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [Hi-C]

2024-01-30 | GSE235558 | GEO

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [ChIP-seq]

2024-01-30 | GSE235557 | GEO

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils.

Project description:Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils.

| PRJNA986453 | ENA

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [ChIP-seq]

Project description:Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [ChIP-seq]

| PRJNA986462 | ENA

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [Hi-C]

Project description:Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [Hi-C]

| PRJNA986466 | ENA

Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [RNA-seq]

Project description:Loop-extruding Smc5/6 organizes transcription-induced positive DNA supercoils [RNA-seq]

| PRJNA986465 | ENA

Human Smc5/6 recognizes transcription-generated positive DNA supercoils

Project description:Beyond its essential roles in ensuring faithful chromosome segregation and genomic stability, the human Smc5/6 complex acts as an antiviral factor. It binds to and impedes the transcription of extrachromosomal DNA templates; an ability which is lost upon chromosomal DNA integration. How the complex distinguishes among different DNA templates is unknown. Here we show that, in human cells, Smc5/6 preferentially binds to circular rather than linear extrachromosomal DNA. We further show that this binding is unlikely due to differences in the chromatin composition. Instead, the transcriptional process, per se, and more specifically the accumulation of DNA secondary structures known to be substrates for topoisomerases, is responsible for Smc5/6 recruitment. Those findings, in conjunction with our genome-wide Smc5/6 binding analysis showing that Smc5/6 localises at few but highly transcribe chromosome loci, reveal a previously unforeseen role of Smc5/6 in DNA topology management during transcription.

2024-06-10 | GSE231328 | GEO

Human Smc5/6 recognizes transcription-generated positive DNA supercoils

Project description:Human Smc5/6 recognizes transcription-generated positive DNA supercoils

| PRJNA963774 | ENA

Centromeric nucleosomes induce positive DNA supercoils.

Project description:Centromeres of higher eukaryotes are epigenetically maintained; however, the mechanism that underlies centromere inheritance is unknown. Centromere identity and inheritance require the assembly of nucleosomes containing the CenH3 histone variant in place of canonical H3. Although H3 nucleosomes wrap DNA in a left-handed manner and induce negative supercoils, we show here that CenH3 nucleosomes reconstituted from Drosophila histones induce positive supercoils. Furthermore, we show that CenH3 likewise induces positive supercoils in functional centromeres in vivo, using a budding yeast minichromosome system and temperature-sensitive mutations in kinetochore proteins. The right-handed wrapping of DNA around the histone core implied by positive supercoiling indicates that centromere nucleosomes are unlikely to be octameric and that the exposed surfaces holding the nucleosome together would be available for kinetochore protein recruitment. The mutual incompatibility of nucleosomes with opposite topologies could explain how centromeres are efficiently maintained as unique loci on chromosomes.

| S-EPMC2725230 | biostudies-literature

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