Academic Journal
CNOT6:A Novel Regulator of DNA Mismatch Repair
| العنوان: | CNOT6:A Novel Regulator of DNA Mismatch Repair |
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| المؤلفون: | Song, Peng, Liu, Shaojun, Liu, Dekang, Keijzers, Guido, Bakula, Daniela, Duan, Shunlei, de Wind, Niels, Ye, Zilu, Vakhrushev, Sergey Y., Scheibye-Knudsen, Morten, Rasmussen, Lene Juel |
| المصدر: | Song , P , Liu , S , Liu , D , Keijzers , G , Bakula , D , Duan , S , de Wind , N , Ye , Z , Vakhrushev , S Y , Scheibye-Knudsen , M & Rasmussen , L J 2022 , ' CNOT6 : A Novel Regulator of DNA Mismatch Repair ' , Cells , vol. 11 , no. 3 , 521 . https://doi.org/10.3390/cells11030521 |
| سنة النشر: | 2022 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | Cancer, Gene regulation, Genome stability, Mammalian deadenylase, Mismatch repair, MRNA degradation |
| الوصف: | DNA mismatch repair (MMR) is a highly conserved pathway that corrects both base–base mispairs and insertion-deletion loops (IDLs) generated during DNA replication. Defects in MMR have been linked to carcinogenesis and drug resistance. However, the regulation of MMR is poorly understood. Interestingly, CNOT6 is one of four deadenylase subunits in the conserved CCR4-NOT complex and it targets poly(A) tails of mRNAs for degradation. CNOT6 is overexpressed in acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and androgen-independent prostate cancer cells, which suggests that an altered expression of CNOT6 may play a role in tumorigenesis. Here, we report that a depletion of CNOT6 sensitizes human U2OS cells to N-methyl-N′nitro-N-nitrosoguanidine (MNNG) and leads to enhanced apoptosis. We also demonstrate that the depletion of CNOT6 upregulates MMR and decreases the mutation frequency in MMR-proficient cells. Furthermore, the depletion of CNOT6 increases the stability of mRNA transcripts from MMR genes, leading to the increased expression of MMR proteins. Our work provides insight into a novel CNOT6-dependent mechanism for regulating MMR. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.3390/cells11030521 |
| الاتاحة: | https://researchprofiles.ku.dk/da/publications/cnot6(4a73b79d-53ab-4fee-9c7d-5acdecd69f44).html https://doi.org/10.3390/cells11030521 https://curis.ku.dk/ws/files/291600986/cells_11_00521_v3.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.3BE1220 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cells11030521 |
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