Cargando…
PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination
Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand bre...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344794/ https://www.ncbi.nlm.nih.gov/pubmed/28238654 http://dx.doi.org/10.1016/j.molcel.2017.01.019 |
_version_ | 1782513593427689472 |
---|---|
author | Clarke, Thomas L. Sanchez-Bailon, Maria Pilar Chiang, Kelly Reynolds, John J. Herrero-Ruiz, Joaquin Bandeiras, Tiago M. Matias, Pedro M. Maslen, Sarah L. Skehel, J. Mark Stewart, Grant S. Davies, Clare C. |
author_facet | Clarke, Thomas L. Sanchez-Bailon, Maria Pilar Chiang, Kelly Reynolds, John J. Herrero-Ruiz, Joaquin Bandeiras, Tiago M. Matias, Pedro M. Maslen, Sarah L. Skehel, J. Mark Stewart, Grant S. Davies, Clare C. |
author_sort | Clarke, Thomas L. |
collection | PubMed |
description | Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand break (DSB) repair, which is mediated through its ability to methylate RUVBL1, a cofactor of the TIP60 complex. We show that PRMT5 targets RUVBL1 for methylation at position R205, which facilitates TIP60-dependent mobilization of 53BP1 from DNA breaks, promoting HR. Mechanistically, we demonstrate that PRMT5-directed methylation of RUVBL1 is critically required for the acetyltransferase activity of TIP60, promoting histone H4K16 acetylation, which facilities 53BP1 displacement from DSBs. Interestingly, RUVBL1 methylation did not affect the ability of TIP60 to facilitate ATM activation. Taken together, our findings reveal the importance of PRMT5-mediated arginine methylation during DSB repair pathway choice through its ability to regulate acetylation-dependent control of 53BP1 localization. |
format | Online Article Text |
id | pubmed-5344794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53447942017-03-17 PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination Clarke, Thomas L. Sanchez-Bailon, Maria Pilar Chiang, Kelly Reynolds, John J. Herrero-Ruiz, Joaquin Bandeiras, Tiago M. Matias, Pedro M. Maslen, Sarah L. Skehel, J. Mark Stewart, Grant S. Davies, Clare C. Mol Cell Article Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand break (DSB) repair, which is mediated through its ability to methylate RUVBL1, a cofactor of the TIP60 complex. We show that PRMT5 targets RUVBL1 for methylation at position R205, which facilitates TIP60-dependent mobilization of 53BP1 from DNA breaks, promoting HR. Mechanistically, we demonstrate that PRMT5-directed methylation of RUVBL1 is critically required for the acetyltransferase activity of TIP60, promoting histone H4K16 acetylation, which facilities 53BP1 displacement from DSBs. Interestingly, RUVBL1 methylation did not affect the ability of TIP60 to facilitate ATM activation. Taken together, our findings reveal the importance of PRMT5-mediated arginine methylation during DSB repair pathway choice through its ability to regulate acetylation-dependent control of 53BP1 localization. Cell Press 2017-03-02 /pmc/articles/PMC5344794/ /pubmed/28238654 http://dx.doi.org/10.1016/j.molcel.2017.01.019 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Clarke, Thomas L. Sanchez-Bailon, Maria Pilar Chiang, Kelly Reynolds, John J. Herrero-Ruiz, Joaquin Bandeiras, Tiago M. Matias, Pedro M. Maslen, Sarah L. Skehel, J. Mark Stewart, Grant S. Davies, Clare C. PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination |
title | PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination |
title_full | PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination |
title_fullStr | PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination |
title_full_unstemmed | PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination |
title_short | PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination |
title_sort | prmt5-dependent methylation of the tip60 coactivator ruvbl1 is a key regulator of homologous recombination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344794/ https://www.ncbi.nlm.nih.gov/pubmed/28238654 http://dx.doi.org/10.1016/j.molcel.2017.01.019 |
work_keys_str_mv | AT clarkethomasl prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT sanchezbailonmariapilar prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT chiangkelly prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT reynoldsjohnj prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT herreroruizjoaquin prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT bandeirastiagom prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT matiaspedrom prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT maslensarahl prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT skeheljmark prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT stewartgrants prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination AT daviesclarec prmt5dependentmethylationofthetip60coactivatorruvbl1isakeyregulatorofhomologousrecombination |