| LEEKSMA, A.C., I.A.M. DERKS, M.H. KASEM, E. KILIC, A. DE KLEIN, M.J. JAGER, A.A. VAN DE LOOSDRECHT, J.H. JANSEN, Veronika NAVRKALOVÁ, L.M. FABER, N. ZABORSKY, A. EGLE, T. ZENZ, Šárka POSPÍŠILOVÁ, O. ABDEL-WAHAB, A.P. KATER and E. ELDERING. The Effect of SF3B1 Mutation on the DNA Damage Response and Nonsense-Mediated mRNA Decay in Cancer. Frontiers in Oncology. Lausanne: Frontiers Media S.A., 2021, vol. 10, JAN, p. 609409-609415. ISSN 2234-943X. Available from: https://dx.doi.org/10.3389/fonc.2020.609409. |
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@article{1782162,
author = {Leeksma, A.C. and Derks, I.A.M. and Kasem, M.H. and Kilic, E. and de Klein, A. and Jager, M.J. and van de Loosdrecht, A.A. and Jansen, J.H. and Navrkalová, Veronika and Faber, L.M. and Zaborsky, N. and Egle, A. and Zenz, T. and Pospíšilová, Šárka and AbdelandWahab, O. and Kater, A.P. and Eldering, E.},
article_location = {Lausanne},
article_number = {JAN},
doi = {http://dx.doi.org/10.3389/fonc.2020.609409},
keywords = {DNA damage response; splicing; nonsense-mediated mRNA decay; apoptosis},
language = {eng},
issn = {2234-943X},
journal = {Frontiers in Oncology},
title = {The Effect of SF3B1 Mutation on the DNA Damage Response and Nonsense-Mediated mRNA Decay in Cancer},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2020.609409/full},
volume = {10},
year = {2021}
}
TY - JOUR
ID - 1782162
AU - Leeksma, A.C. - Derks, I.A.M. - Kasem, M.H. - Kilic, E. - de Klein, A. - Jager, M.J. - van de Loosdrecht, A.A. - Jansen, J.H. - Navrkalová, Veronika - Faber, L.M. - Zaborsky, N. - Egle, A. - Zenz, T. - Pospíšilová, Šárka - Abdel-Wahab, O. - Kater, A.P. - Eldering, E.
PY - 2021
TI - The Effect of SF3B1 Mutation on the DNA Damage Response and Nonsense-Mediated mRNA Decay in Cancer
JF - Frontiers in Oncology
VL - 10
IS - JAN
SP - 609409
EP - 609409
PB - Frontiers Media S.A.
SN - 2234943X
KW - DNA damage response
KW - splicing
KW - nonsense-mediated mRNA decay
KW - apoptosis
UR - https://www.frontiersin.org/articles/10.3389/fonc.2020.609409/full
N2 - 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.
ER -
LEEKSMA, A.C., I.A.M. DERKS, M.H. KASEM, E. KILIC, A. DE KLEIN, M.J. JAGER, A.A. VAN DE LOOSDRECHT, J.H. JANSEN, Veronika NAVRKALOVÁ, L.M. FABER, N. ZABORSKY, A. EGLE, T. ZENZ, Šárka POSPÍŠILOVÁ, O. ABDEL-WAHAB, A.P. KATER and E. ELDERING. The Effect of SF3B1 Mutation on the DNA Damage Response and Nonsense-Mediated mRNA Decay in Cancer. \textit{Frontiers in Oncology}. Lausanne: Frontiers Media S.A., 2021, vol.~10, JAN, p.~609409-609415. ISSN~2234-943X. Available from: https://dx.doi.org/10.3389/fonc.2020.609409.
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