Inducing cellular senescence in vitro by using genetically encoded photosensitizers.

Abstract:

:Cellular senescence, a form of cell cycle arrest, is one of the cellular responses to different types of exogenous and endogenous damage. The senescence phenotype can be induced in vitro by oncogene overexpression and/or DNA damage. Recently, we have reported a novel mechanism of cellular senescence induction by mild genotoxic stress. Specifically, we have shown that the formation of a small number of DNA lesions in normal and cancer cells during S phase leads to cellular senescence-like arrest within the same cell cycle. Here, based on this mechanism, we suggest an approach to remotely induce premature senescence in human cell cultures using short-term light irradiation. We used the genetically encoded photosensitizers, tandem KillerRed and miniSOG, targeted to chromatin by fusion to core histone H2B to induce moderate levels of DNA damage by light in S phase cells. We showed that the cells that express the H2B-fused photosensitizers acquire a senescence phenotype upon illumination with the appropriate light source. Furthermore, we demonstrated that both chromatin-targeted tandem KillerRed (produces O2¯) and miniSOG (produces 1O2) induce single-stranded DNA breaks upon light illumination. Interestingly, miniSOG was also able to induce double-stranded DNA breaks.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Petrova NV,Luzhin AV,Serebrovskaya EO,Ryumina AP,Velichko AK,Razin SV,Kantidze OL

doi

10.18632/aging.101065

subject

Has Abstract

pub_date

2016-10-14 00:00:00

pages

2449-2462

issue

10

issn

1945-4589

pii

101065

journal_volume

8

pub_type

杂志文章

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