Lysosome-mediated processing of chromatin in senescence

Ivanov, A. et al. (2013) Lysosome-mediated processing of chromatin in senescence. Journal of Cell Biology, 202(1), pp. 129-143. (doi: 10.1083/jcb.201212110) (PMID:23816621) (PMCID:PMC3704985)

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Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Pawlikowski, Mr Jeff and Ivanov, Dr Andrejs and Rai, Dr Taranjit and Nelson, Mr David and Manoharan, Miss Indrani and Adams, Professor Peter and van Tuyn, Dr John
Authors: Ivanov, A., Pawlikowski, J., Manoharan, I., van Tuyn, J., Nelson, D.M., Rai, T.S., Shah, P.P., Hewitt, G., Korolchuk, V.I., Passos, J.F., Wu, H., Berger, S.L., and Adams, P.D.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Journal of Cell Biology
Publisher:Rockefeller University Press
ISSN (Online):1540-8140
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Journal of Cell Biology 202(1):129-143
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
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