The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2(NIPBL)/Scc4(Mau2) (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesin loading is essential for cell division, and partial defects cause chromosome missegregation and aberrant transcriptional regulation, leading to severe developmental defects in multicellular organisms. We present here a crystal structure showing the interaction between Scc2 and Scc4. Scc4 is a TPR array that envelops an extended Scc2 peptide. Using budding yeast, we demonstrate that a conserved patch on the surface of Scc4 is required to recruit Scc2/4 to centromeres and to build pericentromeric cohesion. These findings reveal the role of Scc4 in determining the localization of cohesin loading and establish a molecular basis for Scc2/4 recruitment to centromeres.
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http://dx.doi.org/10.7554/eLife.06057 | DOI Listing |
Curr Opin Struct Biol
December 2024
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 41 Medlars Drive, Bethesda, MD 20892, USA. Electronic address:
Chromatin organization, facilitated by compartmentalization and loop extrusion, is crucial for proper gene expression and cell viability. Transcription has long been considered important for shaping genome architecture due to its pervasive activity across the genome and impact on the local chromatin environment. Although earlier studies suggested a minimal contribution of transcription to shaping global genome structure, recent insights from high-resolution chromatin contact mapping, polymer simulations, and acute perturbations have revealed its critical role in dynamic chromatin organization at the level of active genes and enhancer-promoter interactions.
View Article and Find Full Text PDFNat Genet
October 2024
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, New Cornerstone Science Laboratory, School of Life Sciences, Tsinghua University, Beijing, China.
X chromosome inactivation triggers a dramatic reprogramming of transcription and chromosome architecture. However, how the chromatin organization of inactive X chromosome is established de novo in vivo remains elusive. Here, we identified an Xist-separated megadomain structure (X-megadomains) on the inactive X chromosome in mouse extraembryonic lineages and extraembryonic endoderm (XEN) cell lines, and transiently in the embryonic lineages, before Dxz4-delineated megadomain formation at later stages in a strain-specific manner.
View Article and Find Full Text PDFEMBO Rep
September 2024
Department of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Yata 1111, Mishima, Shizuoka, 411-8540, Japan.
Acute protein knockdown is a powerful approach to dissecting protein function in dynamic cellular processes. We previously reported an improved auxin-inducible degron system, AID2, but recently noted that its ability to induce degradation of some essential replication factors, such as ORC1 and CDC6, was not enough to induce lethality. Here, we present combinational degron technologies to control two proteins or enhance target depletion.
View Article and Find Full Text PDFCell Mol Life Sci
August 2024
Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.
Background: Chromosome stability is crucial for homeostasis of pluripotent stem cells (PSCs) and early-stage embryonic development. Chromosomal defects may raise carcinogenic risks in regenerative medicine when using PSCs as original materials. However, the detailed mechanism regarding PSCs chromosome stability maintenance is not fully understood.
View Article and Find Full Text PDFBioessays
October 2024
Biochemistry and Molecular Biotechnology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Cohesin is a ring-shaped complex that is loaded on DNA in two different conformations. In one conformation, it forms loops to organize the interphase genome; in the other, it topologically encircles sibling chromosomes to facilitate homologous recombination and to establish the cohesion that is required for orderly segregation during mitosis. How, and even if, these two loading conformation are related is unclear.
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