Scientific Publications

Reduced histone biosynthesis and chromatin changes arising from a damage signal at telomeres.

Publication TypeJournal Article
AuthorsO'Sullivan, RJ, Kubicek S., Schreiber SL, and Karlseder J.
AbstractDuring replicative aging of primary cells morphological transformations occur, the expression pattern is altered and chromatin changes globally. Here we show that chronic damage signals, probably caused by telomere processing, affect expression of histones and lead to their depletion. We investigated the abundance and cell cycle expression of histones and histone chaperones and found defects in histone biosynthesis during replicative aging. Simultaneously, epigenetic marks were redistributed across the phases of the cell cycle and the DNA damage response (DDR) machinery was activated. The age-dependent reprogramming affected telomeric chromatin itself, which was progressively destabilized, leading to a boost of the telomere-associated DDR with each successive cell cycle. We propose a mechanism in which changes in the structural and epigenetic integrity of telomeres affect core histones and their chaperones, enforcing a self-perpetuating pathway of global epigenetic changes that ultimately leads to senescence.
Year of Publication2010
JournalNature structural & molecular biology
Volume17
Issue10
Pages1218-25
Date Published (YYYY/MM/DD)2010/10/01
ISSN Number1545-9993
DOI10.1038/nsmb.1897
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/20890289?dopt=Abstract