Histone variant H2A.Z has a conserved role in genome stability, although it remains unclear how this is mediated. Here we demonstrate that the fission yeast Swr1 ATPase inserts H2A.Z (Pht1) into chromatin and Kat5 acetyltransferase (Mst1) acetylates it. Deletion or an unacetylatable mutation of Pht1 leads to genome instability, primarily caused by chromosome entanglement and breakage at anaphase. This leads to the loss of telomere-proximal markers, though telomere protection and repeat length are unaffected by the absence of Pht1. Strikingly, the chromosome entanglement in pht1Delta anaphase cells can be rescued by forcing chromosome condensation before anaphase onset. We show that the condensin complex, required for the maintenance of anaphase chromosome condensation, prematurely dissociates from chromatin in the absence of Pht1. This and other findings suggest an important role for H2A.Z in the architecture of anaphase chromosomes.
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http://dx.doi.org/10.1038/nsmb.1688 | DOI Listing |
Cell
November 2024
Institute for Medical Engineering and Science and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address:
Every cell must solve the problem of how to fold its genome. We describe how the folded state of chromosomes is the result of the combined activity of multiple conserved mechanisms. Homotypic affinity-driven interactions lead to spatial partitioning of active and inactive loci.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Physics & LASSP, Cornell University, Ithaca, NY 14853, USA.
Topoisomerase II (topo II) enzymes are essential enzymes known to resolve topological entanglements during DNA processing. Curiously, while yeast expresses a single topo II, humans express two topo II isozymes, topo IIα and topo IIβ, which share a similar catalytic domain but differ in their intrinsically disordered C-terminal domains (CTDs). During mitosis, topo IIα and condensin I constitute the most abundant chromosome scaffolding proteins essential for chromosome condensation.
View Article and Find Full Text PDFNature
October 2024
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
A central feature of meiosis is the pairing of homologous maternal and paternal chromosomes ('homologues') along their lengths. Recognition between homologues and their juxtaposition in space is mediated by axis-associated recombination complexes. Also, pairing must occur without entanglements among unrelated chromosomes.
View Article and Find Full Text PDFNat Mater
November 2024
Department of Physics and Astronomy and LaserLaB, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
During mitosis in eukaryotic cells, mechanical forces generated by the mitotic spindle pull the sister chromatids into the nascent daughter cells. How do mitotic chromosomes achieve the necessary mechanical stiffness and stability to maintain their integrity under these forces? Here we use optical tweezers to show that ions involved in physiological chromosome condensation are crucial for chromosomal stability, stiffness and viscous dissipation. We combine these experiments with high-salt histone depletion and theory to show that chromosomal elasticity originates from the chromatin fibre behaving as a flexible polymer, whereas energy dissipation can be explained by modelling chromatin loops as an entangled polymer solution.
View Article and Find Full Text PDFBiomaterials
February 2025
New Cornerstone Science Laboratory, MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China. Electronic address:
Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment.
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