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Methylation of the central transcriptional regulator KLF4 by PRMT5 is required for DNA end resection and recombination
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Cell fitness and survival upon exposure to DNA damage depends on the repair of DNA lesions. Interestingly, cellular identity does affect and finetunes such response, although the molecular basis of such differences between tissues and cell types is not well understood. Thus, a possibility is that DNA repair itself is controlled by the mechanisms that govern cell identity. Here we show that the KLF4, involved in cellular homeostasis, proliferation, cell reprogramming and cancer development, directly regulates resection and homologous recombination proficiency. Indeed, resection efficiency follows KLF4 protein levels, i.e. decreases upon KLF4 downregulation and increases when is overexpressed. Moreover, KLF4 role in resection requires its methylation by the methyl-transferase PRMT5. Thus, PRMT5 depletion not only mimics KLF4 downregulation, but also showed an epistatic genetic relationship. Our data support a model in which the methylation of KLF4 by PRMT5 is a priming event required to license DNA resection and homologous recombination.<br />This work was funded by R+D+I grants from the Spanish Ministry of Economy and Competitivity (SAF2013-43255-P, SAF2016-74855-P). FR-B is funded by the University of Sevillathrough a postdoctoral contract of the V PPIT-US. CABIMER is supported by the regional government of Andalucia (Junta de Andalucía).
- Subjects :
- Protein-Arginine N-Methyltransferases
DNA End-Joining Repair
DNA end resection
DNA damage
DNA repair
Kruppel-Like Transcription Factors
Cellular homeostasis
Biology
Methylation
Biochemistry
Kruppel-Like Factor 4
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
stomatognathic system
Downregulation and upregulation
Cell Line, Tumor
Humans
DNA Breaks, Double-Stranded
Molecular Biology
030304 developmental biology
0303 health sciences
Recombinational DNA Repair
Epistasis, Genetic
DNA
Cell Biology
KLF4
Recombination
Cell biology
Gene Expression Regulation
chemistry
030220 oncology & carcinogenesis
embryonic structures
PRMT5
sense organs
Homologous recombination
Protein Processing, Post-Translational
Reprogramming
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....546c3b380d24bc7b21a9be2841b61e38