Distinct cellular responses to replication stress leading to apoptosis or senescence
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00541682" target="_blank" >RIV/60162694:G44__/19:00541682 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/19:00510201 RIV/00216224:14110/19:00108131 RIV/00216208:11150/19:10403618
Result on the web
<a href="https://febs.onlinelibrary.wiley.com/doi/10.1002/2211-5463.12632" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/10.1002/2211-5463.12632</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/2211-5463.12632" target="_blank" >10.1002/2211-5463.12632</a>
Alternative languages
Result language
angličtina
Original language name
Distinct cellular responses to replication stress leading to apoptosis or senescence
Original language description
Replication stress (RS) is a major driver of genomic instability and tumorigenesis. Here, we investigated whether RS induced by the nucleotide analog fludarabine and specific kinase inhibitors [e.g. targeting checkpoint kinase 1 (Chk1) or ataxia telangiectasia and Rad3-related (ATR)] led to apoptosis or senescence in four cancer cell lines differing in TP53 mutation status and expression of lamin A/C (LA/C). RS resulted in uneven chromatin condensation in all cell types, as evidenced by the presence of metaphasic chromosomes with unrepaired DNA damage, as well as detection of less condensed chromatin in the same nucleus, frequent ultrafine anaphase bridges, and micronuclei. We observed that responses to these chromatin changes may be distinct in individual cell types, suggesting that expression of lamin A/C and lamin B1 (LB1) may play an important role in the transition of damaged cells to senescence. MCF7 mammary carcinoma cells harboring wild-type p53 (WT-p53) and LA/C responded to RS by transition to senescence with a significant reduction of lamin B receptor and LB1 proteins. In contrast, a lymphoid cancer cell line WSU-NHL (WT-p53) lacking LA/C and expressing low levels of LB1 died after several hours, while lines MEC-1 and SU-DHL-4, both with mutated p53, and SU-DHL-4 with mutations in LA/C, died at different rates by apoptosis. Our results show that, in addition to being influenced by p53 mutation status, the response to RS (apoptosis or senescence) may also be influenced by lamin A/C and LB1 status.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
FEBS Open Bio
ISSN
2211-5463
e-ISSN
2211-5463
Volume of the periodical
9
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
870-890
UT code for WoS article
000477024500003
EID of the result in the Scopus database
2-s2.0-85065017507