PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes
Summary: DNA double-strand break (DSB) repair is critical for cell survival and genome integrity. Upon recognition of DSBs, repair proteins are transiently upregulated to facilitate repair through homologous recombination (HR) or non-homologous end joining (NHEJ). We present evidence that PRMT5 coop...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-01-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900421930495X |
| _version_ | 1818683331673325568 |
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| author | Jake L. Owens Elena Beketova Sheng Liu Samantha L. Tinsley Andrew M. Asberry Xuehong Deng Jiaoti Huang Chenglong Li Jun Wan Chang-Deng Hu |
| author_facet | Jake L. Owens Elena Beketova Sheng Liu Samantha L. Tinsley Andrew M. Asberry Xuehong Deng Jiaoti Huang Chenglong Li Jun Wan Chang-Deng Hu |
| author_sort | Jake L. Owens |
| collection | DOAJ |
| description | Summary: DNA double-strand break (DSB) repair is critical for cell survival and genome integrity. Upon recognition of DSBs, repair proteins are transiently upregulated to facilitate repair through homologous recombination (HR) or non-homologous end joining (NHEJ). We present evidence that PRMT5 cooperates with pICln to function as a master epigenetic activator of DNA damage response (DDR) genes involved in HR, NHEJ, and G2 arrest (including RAD51, BRCA1, and BRCA2) to upregulate gene expression upon DNA damage. Contrary to the predominant role of PRMT5 as an epigenetic repressor, our results demonstrate that PRMT5 and pICln can activate gene expression, potentially independent of PRMT5's obligate cofactor MEP50. Targeting PRMT5 or pICln hinders repair of DSBs in multiple cancer cell lines, and both PRMT5 and pICln expression positively correlates with DDR genes across 32 clinical cancer datasets. Thus, targeting PRMT5 or pICln may be explored in combination with radiation or chemotherapy for cancer treatment. : Molecular Genetics; Molecular Biology; Molecular Mechanism of Gene Regulation Subject Areas: Molecular Genetics, Molecular Biology, Molecular Mechanism of Gene Regulation |
| first_indexed | 2024-12-17T10:33:03Z |
| format | Article |
| id | doaj.art-03bc45484f3543639546952e8afed5eb |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-17T10:33:03Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-03bc45484f3543639546952e8afed5eb2022-12-21T21:52:28ZengElsevieriScience2589-00422020-01-01231PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair GenesJake L. Owens0Elena Beketova1Sheng Liu2Samantha L. Tinsley3Andrew M. Asberry4Xuehong Deng5Jiaoti Huang6Chenglong Li7Jun Wan8Chang-Deng Hu9Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USADepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; Purdue University Interdisciplinary Life Sciences Graduate Program, Purdue University, West Lafayette, IN 47907, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; The Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN 46202, USADepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; Purdue University Interdisciplinary Life Sciences Graduate Program, Purdue University, West Lafayette, IN 47907, USADepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; Purdue University Interdisciplinary Life Sciences Graduate Program, Purdue University, West Lafayette, IN 47907, USADepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USADepartment of Pathology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicinal Chemistry, University of Florida College of Pharmacy, Gainesville, FL 32610, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; The Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN 46202, USA; The Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of BioHealth Informatics, Indiana University School of Informatics and Computing, Indiana University – Purdue University Indianapolis, Indianapolis, IN 46202, USA; Corresponding authorDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA; Corresponding authorSummary: DNA double-strand break (DSB) repair is critical for cell survival and genome integrity. Upon recognition of DSBs, repair proteins are transiently upregulated to facilitate repair through homologous recombination (HR) or non-homologous end joining (NHEJ). We present evidence that PRMT5 cooperates with pICln to function as a master epigenetic activator of DNA damage response (DDR) genes involved in HR, NHEJ, and G2 arrest (including RAD51, BRCA1, and BRCA2) to upregulate gene expression upon DNA damage. Contrary to the predominant role of PRMT5 as an epigenetic repressor, our results demonstrate that PRMT5 and pICln can activate gene expression, potentially independent of PRMT5's obligate cofactor MEP50. Targeting PRMT5 or pICln hinders repair of DSBs in multiple cancer cell lines, and both PRMT5 and pICln expression positively correlates with DDR genes across 32 clinical cancer datasets. Thus, targeting PRMT5 or pICln may be explored in combination with radiation or chemotherapy for cancer treatment. : Molecular Genetics; Molecular Biology; Molecular Mechanism of Gene Regulation Subject Areas: Molecular Genetics, Molecular Biology, Molecular Mechanism of Gene Regulationhttp://www.sciencedirect.com/science/article/pii/S258900421930495X |
| spellingShingle | Jake L. Owens Elena Beketova Sheng Liu Samantha L. Tinsley Andrew M. Asberry Xuehong Deng Jiaoti Huang Chenglong Li Jun Wan Chang-Deng Hu PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes iScience |
| title | PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes |
| title_full | PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes |
| title_fullStr | PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes |
| title_full_unstemmed | PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes |
| title_short | PRMT5 Cooperates with pICln to Function as a Master Epigenetic Activator of DNA Double-Strand Break Repair Genes |
| title_sort | prmt5 cooperates with picln to function as a master epigenetic activator of dna double strand break repair genes |
| url | http://www.sciencedirect.com/science/article/pii/S258900421930495X |
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