Cargando…
Removal of H2A.Z by INO80 promotes homologous recombination
The mammalian INO80 remodelling complex facilitates homologous recombination (HR), but the mechanism by which it does this is unclear. Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. H2A.Z is actively incorporated at sites of damage in mammalian c...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552491/ https://www.ncbi.nlm.nih.gov/pubmed/26142279 http://dx.doi.org/10.15252/embr.201540330 |
_version_ | 1782387735055564800 |
---|---|
author | Alatwi, Hanan E Downs, Jessica A |
author_facet | Alatwi, Hanan E Downs, Jessica A |
author_sort | Alatwi, Hanan E |
collection | PubMed |
description | The mammalian INO80 remodelling complex facilitates homologous recombination (HR), but the mechanism by which it does this is unclear. Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. H2A.Z is actively incorporated at sites of damage in mammalian cells, raising the possibility that H2A.Z may need to be subsequently removed for resolution of repair. Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80. We also report that the histone chaperone ANP32E, which is implicated in removing H2AZ from chromatin, similarly promotes HR and appears to work on the same pathway as INO80 in these assays. Importantly, we demonstrate that the HR defect in cells depleted of INO80 or ANP32E can be rescued by H2A.Z co-depletion, suggesting that H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination. |
format | Online Article Text |
id | pubmed-4552491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-45524912015-12-04 Removal of H2A.Z by INO80 promotes homologous recombination Alatwi, Hanan E Downs, Jessica A EMBO Rep Scientific Reports The mammalian INO80 remodelling complex facilitates homologous recombination (HR), but the mechanism by which it does this is unclear. Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with H2A/H2B dimers. H2A.Z is actively incorporated at sites of damage in mammalian cells, raising the possibility that H2A.Z may need to be subsequently removed for resolution of repair. Here, we show that H2A.Z in human cells is indeed rapidly removed from chromatin flanking DNA damage by INO80. We also report that the histone chaperone ANP32E, which is implicated in removing H2AZ from chromatin, similarly promotes HR and appears to work on the same pathway as INO80 in these assays. Importantly, we demonstrate that the HR defect in cells depleted of INO80 or ANP32E can be rescued by H2A.Z co-depletion, suggesting that H2A.Z removal from chromatin is the primary function of INO80 and ANP32E in promoting homologous recombination. John Wiley & Sons, Ltd 2015-08 2015-07-03 /pmc/articles/PMC4552491/ /pubmed/26142279 http://dx.doi.org/10.15252/embr.201540330 Text en © 2015 The Authors. Published under the terms of the CC BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Scientific Reports Alatwi, Hanan E Downs, Jessica A Removal of H2A.Z by INO80 promotes homologous recombination |
title | Removal of H2A.Z by INO80 promotes homologous recombination |
title_full | Removal of H2A.Z by INO80 promotes homologous recombination |
title_fullStr | Removal of H2A.Z by INO80 promotes homologous recombination |
title_full_unstemmed | Removal of H2A.Z by INO80 promotes homologous recombination |
title_short | Removal of H2A.Z by INO80 promotes homologous recombination |
title_sort | removal of h2a.z by ino80 promotes homologous recombination |
topic | Scientific Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552491/ https://www.ncbi.nlm.nih.gov/pubmed/26142279 http://dx.doi.org/10.15252/embr.201540330 |
work_keys_str_mv | AT alatwihanane removalofh2azbyino80promoteshomologousrecombination AT downsjessicaa removalofh2azbyino80promoteshomologousrecombination |