PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading
The mammalian FBXL10-RNF68-RNF2 ubiquitin ligase complex (FRRUC) mono-ubiquitylates H2A at Lys119 to repress transcription in unstressed cells. We found that the FRRUC is rapidly and transiently recruited to sites of DNA damage in a PARP1- and TIMELESS-dependent manner to promote mono-ubiquitylation...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/38771 |
| _version_ | 1811181023844630528 |
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| author | Gergely Rona Domenico Roberti Yandong Yin Julia K Pagan Harrison Homer Elizabeth Sassani Andras Zeke Luca Busino Eli Rothenberg Michele Pagano |
| author_facet | Gergely Rona Domenico Roberti Yandong Yin Julia K Pagan Harrison Homer Elizabeth Sassani Andras Zeke Luca Busino Eli Rothenberg Michele Pagano |
| author_sort | Gergely Rona |
| collection | DOAJ |
| description | The mammalian FBXL10-RNF68-RNF2 ubiquitin ligase complex (FRRUC) mono-ubiquitylates H2A at Lys119 to repress transcription in unstressed cells. We found that the FRRUC is rapidly and transiently recruited to sites of DNA damage in a PARP1- and TIMELESS-dependent manner to promote mono-ubiquitylation of H2A at Lys119, a local decrease of H2A levels, and an increase of H2A.Z incorporation. Both the FRRUC and H2A.Z promote transcriptional repression, double strand break signaling, and homologous recombination repair (HRR). All these events require both the presence and activity of the FRRUC. Moreover, the FRRUC and its activity are required for the proper recruitment of BMI1-RNF2 and MEL18-RNF2, two other ubiquitin ligases that mono-ubiquitylate Lys119 in H2A upon genotoxic stress. Notably, whereas H2A.Z is not required for H2A mono-ubiquitylation, impairment of the latter results in the inhibition of H2A.Z incorporation. We propose that the recruitment of the FRRUC represents an early and critical regulatory step in HRR. |
| first_indexed | 2024-04-11T09:12:26Z |
| format | Article |
| id | doaj.art-3803e7bc369145b48f3da7f6f1d9bcc1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:26Z |
| publishDate | 2018-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3803e7bc369145b48f3da7f6f1d9bcc12022-12-22T04:32:27ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.38771PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loadingGergely Rona0https://orcid.org/0000-0003-3222-7261Domenico Roberti1Yandong Yin2https://orcid.org/0000-0003-2499-871XJulia K Pagan3Harrison Homer4https://orcid.org/0000-0002-7157-0196Elizabeth Sassani5Andras Zeke6Luca Busino7https://orcid.org/0000-0001-6758-9276Eli Rothenberg8https://orcid.org/0000-0002-1382-1380Michele Pagano9https://orcid.org/0000-0003-3210-2442Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesInstitute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, HungaryDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, United States; Perlmutter Cancer Center, New York University School of Medicine, New York, United States; Howard Hughes Medical Institute, New York University School of Medicine, New York, United StatesThe mammalian FBXL10-RNF68-RNF2 ubiquitin ligase complex (FRRUC) mono-ubiquitylates H2A at Lys119 to repress transcription in unstressed cells. We found that the FRRUC is rapidly and transiently recruited to sites of DNA damage in a PARP1- and TIMELESS-dependent manner to promote mono-ubiquitylation of H2A at Lys119, a local decrease of H2A levels, and an increase of H2A.Z incorporation. Both the FRRUC and H2A.Z promote transcriptional repression, double strand break signaling, and homologous recombination repair (HRR). All these events require both the presence and activity of the FRRUC. Moreover, the FRRUC and its activity are required for the proper recruitment of BMI1-RNF2 and MEL18-RNF2, two other ubiquitin ligases that mono-ubiquitylate Lys119 in H2A upon genotoxic stress. Notably, whereas H2A.Z is not required for H2A mono-ubiquitylation, impairment of the latter results in the inhibition of H2A.Z incorporation. We propose that the recruitment of the FRRUC represents an early and critical regulatory step in HRR.https://elifesciences.org/articles/38771DNA damage responseDNA repairFBXL10RNF68RNF2BMI1 |
| spellingShingle | Gergely Rona Domenico Roberti Yandong Yin Julia K Pagan Harrison Homer Elizabeth Sassani Andras Zeke Luca Busino Eli Rothenberg Michele Pagano PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading eLife DNA damage response DNA repair FBXL10 RNF68 RNF2 BMI1 |
| title | PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading |
| title_full | PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading |
| title_fullStr | PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading |
| title_full_unstemmed | PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading |
| title_short | PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading |
| title_sort | parp1 dependent recruitment of the fbxl10 rnf68 rnf2 ubiquitin ligase to sites of dna damage controls h2a z loading |
| topic | DNA damage response DNA repair FBXL10 RNF68 RNF2 BMI1 |
| url | https://elifesciences.org/articles/38771 |
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