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CNOT6: A Novel Regulator of DNA Mismatch Repair.
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.
Affiliation
  • Song P; Center for Healthy Aging, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Liu S; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Liu D; Department of Spine Surgery, Affiliated Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
  • Keijzers G; Center for Healthy Aging, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Bakula D; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Duan S; Department of Human Anatomy and Histology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • de Wind N; Center for Healthy Aging, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Ye Z; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Vakhrushev SY; Center for Healthy Aging, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Scheibye-Knudsen M; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
  • Rasmussen LJ; Center for Healthy Aging, University of Copenhagen, Copenhagen, DK-2200 Copenhagen, Denmark.
Cells ; 11(3)2022 02 02.
Article in En | MEDLINE | ID: mdl-35159331
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Replication / DNA Mismatch Repair Limits: Humans / Male Language: En Journal: Cells Year: 2022 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Replication / DNA Mismatch Repair Limits: Humans / Male Language: En Journal: Cells Year: 2022 Document type: Article Affiliation country: Country of publication: