Dynamic PML protein nucleolar associations with persistent DNA damage lesions in response to nucleolar stress and senescence-inducing stimuli

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F19%3A00511808" target="_blank" >RIV/68378050:_____/19:00511808 - isvavai.cz</a>

Result on the web

<a href="https://www.aging-us.com/article/102248/text?_escaped_fragment_=" target="_blank" >https://www.aging-us.com/article/102248/text?_escaped_fragment_=</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/aging.102248" target="_blank" >10.18632/aging.102248</a>

Result language

angličtina

Original language name

Dynamic PML protein nucleolar associations with persistent DNA damage lesions in response to nucleolar stress and senescence-inducing stimuli

Original language description

Diverse stress insults trigger interactions of PML with nucleolus, however, the function of these PML nucleolar associations (PNAs) remains unclear. Here we show that during induction of DNA damage-induced senescence in human non-cancerous cells, PML accumulates at the nucleolar periphery simultaneously with inactivation of RNA polymerase I (RNAP I) and nucleolar segregation. Using time-lapse and high-resolution microscopy, we followed the genesis, structural transitions and destiny of PNAs to show that: 1) the dynamic structural changes of the PMLnucleolar interaction are tightly associated with inactivation and reactivation of RNAP I-mediated transcription, respectively, 2) the PML-nucleolar compartment develops sequentially under stress and, upon stress termination, it culminates in either of two fates: disappearance or persistence, 3) all PNAs stages can associate with DNA damage markers, 4) the persistent, commonly long-lasting PML multi-protein nucleolar structures (PML-NDS) associate with markers of DNA damage, indicating a role of PNAs in persistent DNA damage response characteristic for senescent cells. Given the emerging evidence implicating PML in homologous recombination-directed DNA repair, we propose that PNAs contribute to sequestration and faithful repair of the highly unstable ribosomal DNA repeats, a fundamental process to maintain a precise balance between DNA repair mechanisms, with implications for genomic integrity and aging.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/GA17-14743S" target="_blank" >GA17-14743S: Ribosomal stress: mechanisms and relevance to cancer</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Aging

ISSN

1945-4589

e-ISSN

—

Volume of the periodical

11

Issue of the periodical within the volume

17

Country of publishing house

US - UNITED STATES

Number of pages

30

Pages from-to

7206-7235

UT code for WoS article

000487978100041

EID of the result in the Scopus database

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