English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Senescence is triggered by various cellular stresses that result in genomic lesions and DNA damage response activation. However, the role of chromatin and DNA replication in senescence induction remains elusive. Here we show that downregulation of p300 histone acetyltransferase activity induces senescence by a mechanism that is independent of the activation of p53, p21(CIP1) and p16(INK4A). This inhibition leads to a global H3, H4 hypoacetylation, initiating senescence-associated heterochromatic foci formation during S phase, together with a global decrease in replication fork velocity, and alteration of DNA replication timing. This replicative stress occurs without DNA damage and checkpoint activation, but results in a robust G2/M cell cycle arrest, within only one cell cycle. These results provide new insights into the control of S-phase progression by p300, and identify an unexpected chromatin-dependent alternative mechanism for senescence induction, which could possibly be exploited to treat cancer by senescence induction without generating further DNA damage.

p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression