Biology subjects

Haering, C. H.

Publications and source records attributed to Haering, C. H..

6 recordsLinked to original sources

bioRxiv2026

Structural Basis of Condensin Recruitment for X Chromosome Repression

In Caenorhabditis elegans, the condensin IDC complex represses transcription from both X chromosomes in hermaphrodites to achieve dosage compensation. How condensin IDC is specifically recruited to the X chromosomes in coordination with sex determination and dosage compensation (SDC) proteins and how it modulates gene expression have, however, remained unresolved. Here, we identify SDC-3 as the key adaptor that directly binds the elbow coiled-coil domain of the condensin IDC-specific SMC subunit DPY-27. Using cryo-electron microscopy, we determine the structure of the SDC-3 adaptor domain bound to an auto-inhibited condensin IDC holoenzyme. Disrupting this interaction compromises dosage compensation and diminishes condensin IDC enrichment on the X chromosomes. Upon overcoming auto-inhibition, condensin IDC exhibits robust DNA loop-extrusion activity comparable to that of canonical condensin. We propose that SDC-3-anchored condensin IDC exploits loop-extrusion to reorganize X-chromosome chromatin and mediate chromosome-wide transcriptional repression.

biochemistry↗

bioRxiv2021

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

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 in two separate chambers. Single-molecule and cryo-electron microscopy provide evidence for a power-stroke movement at the first chamber that feeds DNA into the SMC-kleisin ring upon ATP binding, while the second chamber holds on upstream of the same DNA double helix. Unlocking the strict separation of motor and anchor chambers turns condensin from a one-sided into a bidirectional DNA loop extruder. We conclude that the orientation of two topologically bound DNA segments during the course of the SMC reaction cycle determines the directionality of DNA loop extrusion.

biochemistry↗

bioRxiv2019

DNA-loop extruding condensin complexes can traverse one another

Condensin, a key member of the Structure Maintenance of Chromosome (SMC) protein complexes, has recently been shown to be a motor that extrudes loops of DNA1. It remains unclear, however, how condensin complexes work together to collectively package DNA into the chromosomal architecture. Here, we use time-lapse single-molecule visualization to study mutual interactions between two DNA-loop-extruding yeast condensins. We find that these one-side-pulling motor proteins are able to dynamically change each others DNA loop sizes, even when located large distances apart. When coming into close proximity upon forming a loop within a loop, condensin complexes are, surprisingly, able to traverse each other and form a new type of loop structure, which we term Z loop - three double-stranded DNA helices aligned in parallel with one condensin at each edge. These Z-loops can fill gaps left by single loops and can form symmetric dimer motors that reel in DNA from both sides. These new findings indicate that condensin may achieve chromosomal compaction using a variety of looping structures.

biophysics↗

bioRxiv2018

Condensin II inactivation in interphase does not affect chromatin folding or gene expression

Condensin complexes have been proposed to play a prominent role in interphase chromatin organization and control of gene expression. Here, we report that the deletion of the central condensin II kleisin subunit Ncaph2 in differentiated mouse hepatocytes does not lead to significant changes in chromosome organization or in gene expression. Both observations challenge current views that implicate condensin in interphase chromosomal domain formation and in enhancer-promoter interactions. Instead, we suggest that the previously reported effects of condensin perturbation may result from their structural role during mitosis, which might indirectly impact the re-establishment of interphase chromosomal architecture after cell division.

genomics↗

bioRxiv2018

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 the mechanisms have remained enigmatic. Here, we report on the role of condensin in gene expression in fission and budding yeasts. In contrast to previous studies, we provide compelling evidence that condensin plays no direct role in the maintenance of the transcriptome, neither during interphase nor during mitosis. We further show that the changes in gene expression in post-mitotic fission yeast cells that result from condensin inactivation are largely a consequence of chromosome missegregation during anaphase, which notably depletes the RNA-exosome from daughter cells. Crucially, preventing karyotype abnormalities in daughter cells restores a normal transcriptome despite condensin inactivation. Thus, chromosome instability, rather than a direct role of condensin in the transcription process, changes gene expression. This knowledge challenges the concept of gene regulation by canonical condensin complexes.

molecular biology↗

bioRxiv2017

Condensin’s ATPase Machinery Drives and Dampens Mitotic Chromosome Condensation

Chromosome condensation by condensin is essential for faithful chromosome segregation. Metazoans have two complexes, named condensin I and II. Both are thought to act by creating looped structures in DNA, but how they do so is unknown. Condensins SMC subunits together form a composite ATPase with two pseudo-symmetric ATPase sites. We reveal that these sites have opposite functions in the condensation process. One site drives condensation, while the other site rather has a dampening function. Mutation of this dampener site hyperactivates both condensin I and II complexes. We find that hyperactive condensin I efficiently shortens chromosomes in the total absence of condensin II. The two complexes form loops with different lengths, and specifically condensin II is key to the decatenation of sister chromatids and the formation of a straight chromosomal axis.

molecular biology↗