The Effect of SF3B1 Mutation on the DNA Damage Response and Nonsense-Mediated mRNA Decay in Cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074398" target="_blank" >RIV/65269705:_____/21:00074398 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14740/21:00119066
Result on the web
<a href="https://www.frontiersin.org/articles/10.3389/fonc.2020.609409/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fonc.2020.609409/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fonc.2020.609409" target="_blank" >10.3389/fonc.2020.609409</a>
Alternative languages
Result language
angličtina
Original language name
The Effect of SF3B1 Mutation on the DNA Damage Response and Nonsense-Mediated mRNA Decay in Cancer
Original language description
Recurrent mutations in splicing factor 3B subunit 1 (SF3B1) have been identified in several malignancies and are associated with an increased expression of 3' cryptic transcripts as a result of alternative branchpoint recognition. A large fraction of cryptic transcripts associated with SF3B1 mutations is expected to be sensitive for RNA degradation via nonsense-mediated mRNA decay (NMD). Several studies indicated alterations in various signaling pathways in SF3B1-mutated cells, including an impaired DNA damage response (DDR) in chronic lymphocytic leukemia (CLL). In this study, we investigated isogenic cell lines and treatment naive primary CLL samples without any TP53 and/or ATM defect, and found no significant effects of SF3B1 mutations on the ATM/p53 response, phosphorylation of H2AX and sensitivity to fludarabine. Cryptic transcripts associated with SF3B1 mutation status were observed at relatively low levels compared to the canonical transcripts and were validated as target for mRNA degradation via NMD. Expression of cryptic transcripts increased after NMD inhibition. In conclusion, our results confirm involvement of NMD in the biological effects of SF3B1 mutations. Further studies may elucidate whether SF3B1-mutant patients could benefit from NMD modulatory agents.
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
30204 - Oncology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Oncology
ISSN
2234-943X
e-ISSN
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Volume of the periodical
10
Issue of the periodical within the volume
JAN 29
Country of publishing house
CH - SWITZERLAND
Number of pages
7
Pages from-to
609409
UT code for WoS article
000617289700001
EID of the result in the Scopus database
2-s2.0-85100865883