Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown.

Autor: Nageshan RK; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. rishi.nageshan@cuanschutz.edu., Ortega R; Department of Molecular Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA., Krogan N; Quantitative Biosciences Institute (QBI), University of California, San Francisco, CA, 94158, USA.; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, 94158, USA.; Gladstone Institute of Data Science and Biotechnology, J. David Gladstone Institutes, San Francisco, CA, 94158, USA., Cooper JP; Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA. julia.p.cooper@cuanschutz.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jun 03; Vol. 15 (1), pp. 4707. Date of Electronic Publication: 2024 Jun 03.
DOI: 10.1038/s41467-024-48382-2
Abstrakt: Persisting replication intermediates can confer mitotic catastrophe. Loss of the fission yeast telomere protein Taz1 (ortholog of mammalian TRF1/TRF2) causes telomeric replication fork (RF) stalling and consequently, telomere entanglements that stretch between segregating mitotic chromosomes. At ≤20 °C, these entanglements fail to resolve, resulting in lethality. Rif1, a conserved DNA replication/repair protein, hinders the resolution of telomere entanglements without affecting their formation. At mitosis, local nuclear envelope (NE) breakdown occurs in the cell's midregion. Here we demonstrate that entanglement resolution occurs in the cytoplasm following this NE breakdown. However, in response to taz1Δ telomeric entanglements, Rif1 delays midregion NE breakdown at ≤20 °C, in turn disfavoring entanglement resolution. Moreover, Rif1 overexpression in an otherwise wild-type setting causes cold-specific NE defects and lethality, which are rescued by membrane fluidization. Hence, NE properties confer the cold-specificity of taz1Δ lethality, which stems from postponement of NE breakdown. We propose that such postponement promotes clearance of simple stalled RFs, but resolution of complex entanglements (involving strand invasion between nonsister telomeres) requires rapid exposure to the cytoplasm.
(© 2024. The Author(s).)
Databáze: MEDLINE
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