Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10412829" target="_blank" >RIV/00216208:11130/20:10412829 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Qd90OGisq9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Qd90OGisq9</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.18632/aging.103453" target="_blank" >10.18632/aging.103453</a>
Alternative languages
Result language
angličtina
Original language name
Telomere attrition and dysfunction: a potential trigger of the progeroid phenotype in nijmegen breakage syndrome
Original language description
Background: Nibrin, as part of the NBN/MRE11/RAD50 complex, is mutated in Nijmegen breakage syndrome (NBS), which leads to impaired DNA damage response and lymphoid malignancy. Results: Telomere length (TL) was markedly reduced in homozygous patients (and comparably so in all chromosomes) by similar to 40% (qPCR) and was slightly reduced in NBS heterozygotes older than 30 years (similar to 25% in qPCR), in accordance with the respective cancer rates. Humanized cancer-free NBS mice had normal TL. Telomere elongation was inducible by telomerase and/or alternative telomere lengthening but was associated with abnormal expression of telomeric genes involved in aging and/or cell growth. Lymphoblastoid cells from NBS patients with long survival times (>12 years) displayed the shortest telomeres and low caspase 7 activity. Conclusions: NBS is a secondary telomeropathy. The two-edged sword of telomere attrition enhances the cancer-prone situation in NBS but can also lead to a relatively stable cellular phenotype in tumor survivors. Results suggest a modular model for progeroid syndromes with abnormal expression of telomeric genes as a molecular basis. Methods: We studied TL and function in 38 homozygous individuals, 27 heterozygotes, one homozygous fetus, six NBS lymphoblastoid cell lines, and humanized NBS mice, all with the same founder NBN mutation: c.657_661del5.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10600 - Biological sciences
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Aging
ISSN
1945-4589
e-ISSN
—
Volume of the periodical
12
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
34
Pages from-to
12342-12375
UT code for WoS article
000548154300016
EID of the result in the Scopus database
2-s2.0-85087363080