Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks

Aymard, François; Bugler, Béatrix; Schmidt, Christine K.; Guillou, Emmanuelle; Caron, Pierre; Briois, Sébastien; Iacovoni, Jason S.; Daburon, Virginie; Miller, Kyle M.; Jackson, Stephen; Legube, Gaëlle

doi:10.1038/nsmb.2796

Cited by 583 publications

(769 citation statements)

References 52 publications

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“…As previously reported in literature (Aymard et al, 2014), γH2AX ChIP-seq signal showed that, upon 4OHT induction, phosphorylation of histone H2AX established a megabaselarge zone of modified chromatin surrounding the AsiSI-DSB ( Figure 1A and B).…”

Section: Drosha Is Recruited To Dsbssupporting

confidence: 59%

“…http://dx.doi.org/10.1101/261289 doi: bioRxiv preprint first posted online Feb. 7, 2018; near the DNA end, a localization which very much resembles that of NHEJ-repair factors such as XRCC4 (Aymard et al, 2014). Consistently, DROSHA accumulates preferentially at NHEJ-prone sites and its association with damaged chromatin is enhanced by NHEJ stimulation and HR suppression, as achieved by CtIP silencing.…”

Section: Discussionmentioning

confidence: 50%

“…A previous study (Aymard et al, 2014) in the DIvA cellular system reported that in G1 the recruitment of the NHEJ factor XRCC4 occurs at all AsiSI induced DSBs, while in G2 RAD51 is recruited at a subset of DSBs. On the basis of RAD51/XRCC4 ratios, this analysis highlighted two subgroups of AsiSI induced DSBs referred as HR-prone and NHEJ-prone sites (Aymard et al, 2014).…”

Section: Drosha Recruitment To Dsbs Is Enhanced By Hr Suppression Andmentioning

confidence: 99%

“…On the basis of RAD51/XRCC4 ratios, this analysis highlighted two subgroups of AsiSI induced DSBs referred as HR-prone and NHEJ-prone sites (Aymard et al, 2014). Thus, we decided to exploit this information to further validate a link between DROSHA and the NHEJ repair pathway.…”

Section: Drosha Recruitment To Dsbs Is Enhanced By Hr Suppression Andmentioning

confidence: 99%

“…To test this hypothesis, we took advantage of the DIvA cellular system (for DSB inducible via AsiSI), (Iacovoni et al, 2010), (Aymard et al, 2014), , (Aymard et al, 2017) a clonal U2OS cell line that stably expresses the AsiSI restriction enzyme fused with a modified oestrogen receptor ligand binding domain. Treatment of cells with 4-OH-Tamoxifen (4-OHT) triggers nuclear localization of the AsiSI enzyme and the generation of hundreds of sequence-specific DSBs uniformly distributed in the genome.…”

Section: Drosha Is Recruited To Dsbsmentioning

confidence: 99%

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DROSHA associates to DNA damage sites and is required for DNA repair

Cabrini

Roncador

Galbiati

et al. 2018

Preprint

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The DNA damage response (DDR) is the signaling cascade through which a cell recognizes DNA lesions, and promotes their resolution via the repair pathways of Non-Homologous End Joining (NHEJ), or Homologous Recombination (HR). We recently demonstrated that DROSHA boosts DDR signaling by processing damage-induced long non-coding RNAs into smaller DNA damage response RNAs (DDRNAs). However, the location at which DROSHA exerts its DDR functions, relative to sites of DNA damage, remains unknown.To investigate DROSHA's localization during DDR activation, we used the DiVA cellular system, which allows the controlled induction of several DNA double strand breaks (DSBs) in the human genome. Indeed, by genome wide chromatin immunoprecipitation followed by next generation sequencing, we demonstrate that DROSHA associates with DSBs. In support of this, DSB-recruitment of DROSHA is detectable at the single-cell level by Proximity Ligation Assay between DROSHA and known DDR markers, and by DNA damage in situ ligation followed by Proximity Ligation Assay (DI-PLA), which demonstrates proximity of DROSHA to DNA ends. DROSHA recruitment occurs at both genic and inter-genic DSBs, suggesting that its recruitment is independent from ongoing transcription preceding damage generation. DROSHA's recruitment to DNA lesions occurs throughout the cell cycle, and with a preference for NHEJ-prone DSBs. Consistently, inhibition of the HR pathway increases DROSHA recruitment, and DROSHA knock down strongly impairs NHEJ efficiency in a GFP-reporter cellular system for monitoring NHEJ DNA repair. Overall, these results demonstrate that DROSHA acts locally at sites of DNA damage to promote NHEJ DNA repair.

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Section: Drosha Is Recruited To Dsbssupporting

confidence: 59%

Section: Discussionmentioning

confidence: 50%

Section: Drosha Recruitment To Dsbs Is Enhanced By Hr Suppression Andmentioning

confidence: 99%

Section: Drosha Recruitment To Dsbs Is Enhanced By Hr Suppression Andmentioning

confidence: 99%

Section: Drosha Is Recruited To Dsbsmentioning

confidence: 99%

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DROSHA associates to DNA damage sites and is required for DNA repair

Cabrini

Roncador

Galbiati

et al. 2018

Preprint

View full text Add to dashboard Cite

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Transcription‐coupled DNA repair protects genome stability upon oxidative stress‐derived DNA strand breaks

Yang,

Lan

2024

FEBS Letters

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Elevated oxidative stress, which threatens genome stability, has been detected in almost all types of cancers. Cells employ various DNA repair pathways to cope with DNA damage induced by oxidative stress. Recently, a lot of studies have provided insights into DNA damage response upon oxidative stress, specifically in the context of transcriptionally active genomes. Here, we summarize recent studies to help understand how the transcription is regulated upon DNA double strand breaks (DSB) and how DNA repair pathways are selectively activated at the damage sites coupling with transcription. The role of RNA molecules, especially R‐loops and RNA modifications during the DNA repair process, is critical for protecting genome stability. This review provides an update on how cells protect transcribed genome loci via transcription‐coupled repair pathways.

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How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between DNA Repair and Transcription

Sivaramakrishnan¹,

Gordon²,

Halliday³

et al. 2018

BioEssays

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Transcription is a fundamental cellular process and the first step in gene regulation. Although RNA polymerase (RNAP) is highly processive, in growing cells the progression of transcription can be hindered by obstacles on the DNA template, such as damaged DNA. The authors recent findings highlight a trade-off between transcription fidelity and DNA break repair. While a lot of work has focused on the interaction between transcription and nucleotide excision repair, less is known about how transcription influences the repair of DNA breaks. The authors suggest that when the cell experiences stress from DNA breaks, the control of RNAP processivity affects the balance between preserving transcription integrity and DNA repair. Here, how the conflict between transcription and DNA double-strand break (DSB) repair threatens the integrity of both RNA and DNA are discussed. In reviewing this field, the authors speculate on cellular paradigms where this equilibrium is well sustained, and instances where the maintenance of transcription fidelity is favored over genome stability.

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Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks

Cited by 583 publications

References 52 publications

DROSHA associates to DNA damage sites and is required for DNA repair

DROSHA associates to DNA damage sites and is required for DNA repair

Transcription‐coupled DNA repair protects genome stability upon oxidative stress‐derived DNA strand breaks

How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between DNA Repair and Transcription

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