Sister chromatid cohesion involves entrapment of sister DNAs by a cohesin ring created through association of a kleisin subunit (Scc1) with ATPase heads of Smc1/Smc3 heterodimers. Cohesin's association with chromatin involves subunits recruited by Scc1: Wapl, Pds5, and Scc3/SA, in addition to Scc2/4 loading complex. Unlike Pds5, Wapl, and Scc2/4, Scc3s are encoded by all eukaryotic genomes. Here, a crystal structure of Scc3 reveals a hook-shaped protein composed of tandem α helices. Its N-terminal domain contains a conserved and essential surface (CES) present even in organisms lacking Pds5, Wapl, and Scc2/4, while its C-terminal domain binds a section of the kleisin Scc1. Scc3 turns over in G2/M while maintaining cohesin's association with chromosomes and it promotes de-acetylation of Smc3 upon Scc1 cleavage.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175184 | PMC |
http://dx.doi.org/10.1016/j.febslet.2014.08.015 | 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 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 PDFNat Commun
January 2025
Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine- Affiliated Renji Hospital, Shanghai, 200127, China.
T cell activation is accompanied by extensive changes in epigenome. However, the high-ordered chromatin organization underpinning CD8 T cell activation is not fully known. Here, we show extensive changes in the three-dimensional genome during CD8 T cell activation, associated with changes in gene transcription.
View Article and Find Full Text PDFThis study aimed to evaluate the impact of the myelodysplasia-related gene (MRG) as well as additional gene mutations on outcomes in intensively treated patients with -mutated ( ) AML. Targeted DNA sequencing of 263 genes was performed in 568 AML patients (median age: 59 years) entered into the prospective AMLSG 09-09 treatment trial. Most commonly co-mutated genes were (49.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!