Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. However, Pds5p and the cohesin complex likely have distinct roles in cohesion. We report that pds5 mutants establish cohesion, but during mitosis exhibit precocious sister dissociation. Thus, unlike the cohesin complex, which is required for cohesion establishment and maintenance, Pds5p is required only for maintenance. We identified SMT4, which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious sister dissociation of pds5 mutants. In contrast, SMT4 does not suppress temperature sensitivity of cohesin complex mutants. Pds5p is SUMO conjugated, with sumoylation peaking during mitosis. SMT4 overexpression reduces Pds5p sumoylation, whereas smt4 mutants have increased Pds5p sumoylation. smt4 mutants were previously shown to be defective in cohesion maintenance during mitosis. These data provide the first link between a protein required for cohesion, Pds5p, and sumoylation, and suggest that Pds5p sumoylation promotes the dissolution of cohesion.
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http://dx.doi.org/10.1083/jcb.200305080 | DOI Listing |
Cells
January 2025
Department of Cancer Biology and Molecular Medicine, City of Hope National Medical Center, Duarte, CA 91010, USA.
Structural maintenance of chromosome-1A (SMC1A) is overexpressed in various malignancies including triple-negative breast cancer (TNBC). As a core component of the cohesin complex, SMC1A was initially recognized for its involvement in chromosomal cohesion and DNA-repair pathways. However, recent studies have unveiled its pivotal role in epithelial-mesenchymal transition (EMT), metastasis, and chemo- and radio-resistance in cancer cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Shenzhen Key Laboratory of Biomolecular Assembling and Regulation, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
Ankyrin Repeat Domain-containing Protein 11 () is a causative gene for KBG syndrome, a significant risk factor for Cornelia de Lange syndrome (CdLS), and a highly confident autism spectrum disorder gene. Mutations of lead to developmental abnormalities in multiple organs/tissues including the brain, craniofacial and skeletal bones, and tooth structures with unknown mechanism(s). Here, we find that ANKRD11, via a short peptide fragment in its N-terminal region, binds to the cohesin complex with a high affinity, implicating why mutation can cause CdLS.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Hematopoietic Biology & Malignancy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cells undergo tens of thousands of DNA-damaging events each day. Defects in repairing double-stranded breaks (DSBs) can lead to genomic instability, contributing to cancer, genetic disorders, immunological diseases, and developmental defects. Cohesin, a multi-subunit protein complex, plays a crucial role in both chromosome organization and DNA repair by creating architectural loops through chromatin extrusion.
View Article and Find Full Text PDFCurr Opin Genet Dev
January 2025
School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; New Cornerstone Science Laboratory, Westlake University, Hangzhou, Zhejiang, China. Electronic address:
Chromosomes in eukaryotic cells undergo compaction at multiple levels and are folded into hierarchical structures to fit into the nucleus with limited dimensions. Three-dimensional genome organization needs to be coordinated with chromosome-templated processes, including DNA replication and gene transcription. As an ATPase molecular machine, the cohesin complex is a major driver of genome folding, which regulates transcription by modulating promoter-enhancer contacts.
View Article and Find Full Text PDFCell
January 2025
Department of Bionanoscience, Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft, the Netherlands. Electronic address:
Structural maintenance of chromosomes (SMC) complexes organize the genome via DNA loop extrusion. Although some SMCs were reported to do so symmetrically, reeling DNA from both sides into the extruded DNA loop simultaneously, others perform loop extrusion asymmetrically toward one direction only. The mechanism underlying this variability remains unclear.
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