Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites.
The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation aff...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-03-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5891081?pdf=render |
| _version_ | 1819104707390472192 |
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| author | Takeshi Yasuda Wataru Kagawa Tomoo Ogi Takamitsu A Kato Takehiro Suzuki Naoshi Dohmae Kazuya Takizawa Yuka Nakazawa Matthew D Genet Mika Saotome Michio Hama Teruaki Konishi Nakako Izumi Nakajima Masaharu Hazawa Masanori Tomita Manabu Koike Katsuko Noshiro Kenichi Tomiyama Chizuka Obara Takaya Gotoh Ayako Ui Akira Fujimori Fumiaki Nakayama Fumio Hanaoka Kaoru Sugasawa Ryuichi Okayasu Penny A Jeggo Katsushi Tajima |
| author_facet | Takeshi Yasuda Wataru Kagawa Tomoo Ogi Takamitsu A Kato Takehiro Suzuki Naoshi Dohmae Kazuya Takizawa Yuka Nakazawa Matthew D Genet Mika Saotome Michio Hama Teruaki Konishi Nakako Izumi Nakajima Masaharu Hazawa Masanori Tomita Manabu Koike Katsuko Noshiro Kenichi Tomiyama Chizuka Obara Takaya Gotoh Ayako Ui Akira Fujimori Fumiaki Nakayama Fumio Hanaoka Kaoru Sugasawa Ryuichi Okayasu Penny A Jeggo Katsushi Tajima |
| author_sort | Takeshi Yasuda |
| collection | DOAJ |
| description | The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism. |
| first_indexed | 2024-12-22T02:10:38Z |
| format | Article |
| id | doaj.art-e1679cb73def4710aa1a8cba50af9b31 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-22T02:10:38Z |
| publishDate | 2018-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-e1679cb73def4710aa1a8cba50af9b312022-12-21T18:42:24ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-03-01143e100727710.1371/journal.pgen.1007277Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites.Takeshi YasudaWataru KagawaTomoo OgiTakamitsu A KatoTakehiro SuzukiNaoshi DohmaeKazuya TakizawaYuka NakazawaMatthew D GenetMika SaotomeMichio HamaTeruaki KonishiNakako Izumi NakajimaMasaharu HazawaMasanori TomitaManabu KoikeKatsuko NoshiroKenichi TomiyamaChizuka ObaraTakaya GotohAyako UiAkira FujimoriFumiaki NakayamaFumio HanaokaKaoru SugasawaRyuichi OkayasuPenny A JeggoKatsushi TajimaThe p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis. An immunofluorescence microscopy analysis revealed that RAD52 acetylation at DSBs sites is counteracted by SIRT2- and SIRT3-mediated deacetylation, and that non-acetylated RAD52 initially accumulates at DSB sites, but dissociates prematurely from them. In the absence of RAD52 acetylation, RAD51, which plays a central role in HR, also dissociates prematurely from DSB sites, and hence HR is impaired. Furthermore, inhibition of ataxia telangiectasia mutated (ATM) protein by siRNA or inhibitor treatment demonstrated that the acetylation of RAD52 at DSB sites is dependent on the ATM protein kinase activity, through the formation of RAD52, p300/CBP, SIRT2, and SIRT3 foci at DSB sites. Our findings clarify the importance of RAD52 acetylation in HR and its underlying mechanism.http://europepmc.org/articles/PMC5891081?pdf=render |
| spellingShingle | Takeshi Yasuda Wataru Kagawa Tomoo Ogi Takamitsu A Kato Takehiro Suzuki Naoshi Dohmae Kazuya Takizawa Yuka Nakazawa Matthew D Genet Mika Saotome Michio Hama Teruaki Konishi Nakako Izumi Nakajima Masaharu Hazawa Masanori Tomita Manabu Koike Katsuko Noshiro Kenichi Tomiyama Chizuka Obara Takaya Gotoh Ayako Ui Akira Fujimori Fumiaki Nakayama Fumio Hanaoka Kaoru Sugasawa Ryuichi Okayasu Penny A Jeggo Katsushi Tajima Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. PLoS Genetics |
| title | Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. |
| title_full | Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. |
| title_fullStr | Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. |
| title_full_unstemmed | Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. |
| title_short | Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. |
| title_sort | novel function of hats and hdacs in homologous recombination through acetylation of human rad52 at double strand break sites |
| url | http://europepmc.org/articles/PMC5891081?pdf=render |
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