Adding a twist to the loops: the role of DNA superhelicity in the organization of chromosomes by SMC protein complexes.

Structural maintenance of chromosomes (SMC) protein complexes, including cohesin, condensin, and the Smc5/6 complex, are integral to various processes in chromosome biology. Despite their distinct roles, these complexes share two key properties: the ability to extrude DNA into large loop structures and the capacity to alter the superhelicity of the DNA double helix. In this review, we explore the influence of eukaryotic SMC complexes on DNA topology, debate its potential physiological function, and discuss new structural insights that may explain how these complexes mediate changes in DNA topology.

Estimating the prevalence of mental disorders in patients with newly diagnosed cancer in relation to socioeconomic status: a multicenter prospective observational study.

Background: The purpose of this study was to provide the 4-week prevalence estimates of mental disorders in newly diagnosed cancer patients in relation to socioeconomic status (SES).

Patients And Methods: We enrolled newly diagnosed patients with a confirmed solid tumor within 2 months of diagnosis. We calculated patients' SES on the basis of their educational level, professional qualification, income and occupational status.

Ovarian Tissue Cryopreservation for Fertility Preservation in Patients with Hemoglobin Disorders: A Comprehensive Review.

Hemoglobin diseases like sickle cell disease (SCD) and β-thalassemia (BT) present fertility challenges for affected patients. SCD and BT result from abnormal hemoglobin production or structure and pose numerous health concerns. Despite medical advancements improving the quality of life or even providing cures, SCD and BT pose unique fertility concerns for women.

How do molecular motors fold the genome?

A potential mechanism of DNA loop extrusion by molecular motors is discussed.

[Impact of Oncological Treatment on Perceived Stigmatization - A Register-Based Study].

Background: Studies on stigmatization of cancer patients show a moderate or high relevance of perceived stigmatization. To date, there are no studies with explicit focus on stigma in relation to oncological therapy. We investigated the role of oncological therapy on perceived stigma in a large sample.

A hold-and-feed mechanism drives directional DNA loop extrusion by condensin.

Structural maintenance of chromosomes (SMC) protein complexes structure genomes by extruding DNA loops, but the molecular mechanism that underlies their activity has remained unknown. We show that the active condensin complex entraps the bases of a DNA loop transiently in two separate chambers. Single-molecule imaging and cryo-electron microscopy suggest a putative power-stroke movement at the first chamber that feeds DNA into the SMC-kleisin ring upon adenosine triphosphate binding, whereas the second chamber holds on upstream of the same DNA double helix.

Hepatitis B virus elimination status and strategies in circumpolar countries, 2020.

Hepatitis B virus (HBV) infection remains a global health threat. The World Health Organization (WHO) established a goal to eliminate HBV infection as a public health threat by 2030, and defined targets for key interventions to achieve that goal. We evaluated HBV burden and relevant national recommendations for progress towards WHO targets in circumpolar countries.

Publisher Correction: The condensin holocomplex cycles dynamically between open and collapsed states.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The condensin holocomplex cycles dynamically between open and collapsed states.

Structural maintenance of chromosome (SMC) protein complexes are the key organizers of the spatiotemporal structure of chromosomes. The condensin SMC complex has recently been shown to be a molecular motor that extrudes large loops of DNA, but the mechanism of this unique motor remains elusive. Using atomic force microscopy, we show that budding yeast condensin exhibits mainly open 'O' shapes and collapsed 'B' shapes, and it cycles dynamically between these two states over time, with ATP binding inducing the O to B transition.

Structural insights into DNA loop extrusion by SMC protein complexes.

Structural Maintenance of Chromosomes (SMC) protein complexes play key roles in the three-dimensional organization of genomes in all kingdoms of life. Recent insights from chromosome contact mapping experiments and single-molecule imaging assays suggest that these complexes achieve distinct cellular functions by extruding large loops of DNA while they move along the chromatin fiber. In this short review, we summarize recent insights into the molecular architecture of these unconventional DNA motor complexes, their interaction with their DNA substrates, and the remarkable dynamic changes they can undergo during their ATPase reaction cycle.

Cryo-EM structures of holo condensin reveal a subunit flip-flop mechanism.

Complexes containing a pair of structural maintenance of chromosomes (SMC) family proteins are fundamental for the three-dimensional (3D) organization of genomes in all domains of life. The eukaryotic SMC complexes cohesin and condensin are thought to fold interphase and mitotic chromosomes, respectively, into large loop domains, although the underlying molecular mechanisms have remained unknown. We used cryo-EM to investigate the nucleotide-driven reaction cycle of condensin from the budding yeast Saccharomyces cerevisiae.

DNA-loop extruding condensin complexes can traverse one another.

Condensin, a key component of the structure maintenance of chromosome (SMC) protein complexes, has recently been shown to be a motor that extrudes loops of DNA. It remains unclear, however, how condensin complexes work together to collectively package DNA into chromosomes. Here we use time-lapse single-molecule visualization to study mutual interactions between two DNA-loop-extruding yeast condensins.

Distinct Roles for Condensin's Two ATPase Sites in Chromosome Condensation.

Condensin is a conserved SMC complex that uses its ATPase machinery to structure genomes, but how it does so is largely unknown. We show that condensin's ATPase has a dual role in chromosome condensation. Mutation of one ATPase site impairs condensation, while mutating the second site results in hyperactive condensin that compacts DNA faster than wild-type, both in vivo and in vitro.

Solution structure and flexibility of the condensin HEAT-repeat subunit Ycg1.

High-resolution structural analysis of flexible proteins is frequently challenging and requires the synergistic application of different experimental techniques. For these proteins, small-angle X-ray scattering (SAXS) allows for a quantitative assessment and modeling of potentially flexible and heterogeneous structural states. Here, we report SAXS characterization of the condensin HEAT-repeat subunit Ycg1 in solution, complementing currently available high-resolution crystallographic models.

Structural Basis of an Asymmetric Condensin ATPase Cycle.

The condensin protein complex plays a key role in the structural organization of genomes. How the ATPase activity of its SMC subunits drives large-scale changes in chromosome topology has remained unknown. Here we reconstruct, at near-atomic resolution, the sequence of events that take place during the condensin ATPase cycle.

Towards a Unified Model of SMC Complex Function.

Protein complexes built of structural maintenance of chromosomes (SMC) and kleisin subunits, including cohesin, condensin and the Smc5/6 complex, are master organizers of genome architecture in all kingdoms of life. How these large ring-shaped molecular machines use the energy of ATP hydrolysis to change the topology of chromatin fibers has remained a central unresolved question of chromosome biology. A currently emerging concept suggests that the common principle that underlies the essential functions of SMC protein complexes in the control of gene expression, chromosome segregation or DNA damage repair is their ability to expand DNA into large loop structures.

Condensin controls cellular RNA levels through the accurate segregation of chromosomes instead of directly regulating transcription.

Condensins are genome organisers that shape chromosomes and promote their accurate transmission. Several studies have also implicated condensins in gene expression, although any mechanisms have remained enigmatic. Here, we report on the role of condensin in gene expression in fission and budding yeasts.

Structural basis for Scc3-dependent cohesin recruitment to chromatin.

The cohesin ring complex is required for numerous chromosomal transactions including sister chromatid cohesion, DNA damage repair and transcriptional regulation. How cohesin engages its chromatin substrate has remained an unresolved question. We show here, by determining a crystal structure of the budding yeast cohesin HEAT-repeat subunit Scc3 bound to a fragment of the Scc1 kleisin subunit and DNA, that Scc3 and Scc1 form a composite DNA interaction module.

Control of mitotic chromosome condensation by the fission yeast transcription factor Zas1.

Although the formation of rod-shaped chromosomes is vital for the correct segregation of eukaryotic genomes during cell divisions, the molecular mechanisms that control the chromosome condensation process have remained largely unknown. Here, we identify the CH zinc-finger transcription factor Zas1 as a key regulator of mitotic condensation dynamics in a quantitative live-cell microscopy screen of the fission yeast By binding to specific DNA target sequences in their promoter regions, Zas1 controls expression of the Cnd1 subunit of the condensin protein complex and several other target genes, whose combined misregulation in mutants results in defects in chromosome condensation and segregation. Genetic and biochemical analysis reveals an evolutionarily conserved transactivation domain motif in Zas1 that is pivotal to its function in gene regulation.

Real-time detection of condensin-driven DNA compaction reveals a multistep binding mechanism.

Condensin, a conserved member of the SMC protein family of ring-shaped multi-subunit protein complexes, is essential for structuring and compacting chromosomes. Despite its key role, its molecular mechanism has remained largely unknown. Here, we employ single-molecule magnetic tweezers to measure, in real time, the compaction of individual DNA molecules by the budding yeast condensin complex.

Two independent modes of chromatin organization revealed by cohesin removal.

Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding.