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J Cell Biol. 2019 Feb 4;218(2):433-444. doi: 10.1083/jcb.201809123. Epub 2018 Dec 14.

Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells.

Author information

1
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA.
2
Department of Pharmacology, University of California, San Diego, La Jolla, CA.
3
National Center for Microscopy and Imaging Research, Center for Research on Biological Systems, University of California, San Diego, La Jolla, CA.
4
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
5
Department of Neurosciences, University of California, San Diego, La Jolla, CA.
6
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA hetzer@salk.edu.

Abstract

Many adult tissues contain postmitotic cells as old as the host organism. The only organelle that does not turn over in these cells is the nucleus, and its maintenance represents a formidable challenge, as it harbors regulatory proteins that persist throughout adulthood. Here we developed strategies to visualize two classes of such long-lived proteins, histones and nucleoporins, to understand the function of protein longevity in nuclear maintenance. Genome-wide mapping of histones revealed specific enrichment of long-lived variants at silent gene loci. Interestingly, nuclear pores are maintained by piecemeal replacement of subunits, resulting in mosaic complexes composed of polypeptides with vastly different ages. In contrast, nondividing quiescent cells remove old nuclear pores in an ESCRT-dependent manner. Our findings reveal distinct molecular strategies of nuclear maintenance, linking lifelong protein persistence to gene regulation and nuclear integrity.

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