DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation
Tudor-interacting repair regulator (TIRR) is an RNA-binding protein and a negative regulator of the DNA-repair factor p53-binding protein 1 (53BP1). In non-damage conditions, TIRR is bound to 53BP1. After DNA damage, TIRR and 53BP1 dissociate, and 53BP1 binds the chromatin at the double-strand break...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2022
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| _version_ | 1826309411994337280 |
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| author | Ketley, RF Battistini, F Alagia, A Mondielli, C Iehl, F Balikçi, E Huber, KVM Orozco, M Gullerova, M |
| author_facet | Ketley, RF Battistini, F Alagia, A Mondielli, C Iehl, F Balikçi, E Huber, KVM Orozco, M Gullerova, M |
| author_sort | Ketley, RF |
| collection | OXFORD |
| description | Tudor-interacting repair regulator (TIRR) is an RNA-binding protein and a negative regulator of the DNA-repair factor p53-binding protein 1 (53BP1). In non-damage conditions, TIRR is bound to 53BP1. After DNA damage, TIRR and 53BP1 dissociate, and 53BP1 binds the chromatin at the double-strand break (DSB) to promote non-homologous end joining (NHEJ)-mediated repair. However, the exact mechanistic details of this dissociation after damage are unknown. Increasing evidence has implicated RNA as a crucial factor in the DNA damage response (DDR). Here, we show that RNA can separate TIRR/53BP1. Specifically, RNA with a hairpin secondary structure, transcribed at the DSB by RNA polymerase II (RNAPII), promotes TIRR/53BP1 complex separation. This hairpin RNA binds to the same residues on TIRR as 53BP1. Our results uncover a role of DNA-damage-derived RNA in modulating a protein-protein interaction and contribute to our understanding of DSB repair. |
| first_indexed | 2024-03-07T07:35:21Z |
| format | Journal article |
| id | oxford-uuid:b8c5c678-6205-4dc1-ae0b-8e138ee8b432 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:35:21Z |
| publishDate | 2022 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:b8c5c678-6205-4dc1-ae0b-8e138ee8b4322023-02-23T10:30:51ZDNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b8c5c678-6205-4dc1-ae0b-8e138ee8b432EnglishSymplectic ElementsCell Press2022Ketley, RFBattistini, FAlagia, AMondielli, CIehl, FBalikçi, EHuber, KVMOrozco, MGullerova, MTudor-interacting repair regulator (TIRR) is an RNA-binding protein and a negative regulator of the DNA-repair factor p53-binding protein 1 (53BP1). In non-damage conditions, TIRR is bound to 53BP1. After DNA damage, TIRR and 53BP1 dissociate, and 53BP1 binds the chromatin at the double-strand break (DSB) to promote non-homologous end joining (NHEJ)-mediated repair. However, the exact mechanistic details of this dissociation after damage are unknown. Increasing evidence has implicated RNA as a crucial factor in the DNA damage response (DDR). Here, we show that RNA can separate TIRR/53BP1. Specifically, RNA with a hairpin secondary structure, transcribed at the DSB by RNA polymerase II (RNAPII), promotes TIRR/53BP1 complex separation. This hairpin RNA binds to the same residues on TIRR as 53BP1. Our results uncover a role of DNA-damage-derived RNA in modulating a protein-protein interaction and contribute to our understanding of DSB repair. |
| spellingShingle | Ketley, RF Battistini, F Alagia, A Mondielli, C Iehl, F Balikçi, E Huber, KVM Orozco, M Gullerova, M DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation |
| title | DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation |
| title_full | DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation |
| title_fullStr | DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation |
| title_full_unstemmed | DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation |
| title_short | DNA double-strand break-derived RNA drives TIRR/53BP1 complex dissociation |
| title_sort | dna double strand break derived rna drives tirr 53bp1 complex dissociation |
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