MRE11-RAD50-NBS1 Complex Is Sufficient to Promote Transcription by RNA Polymerase II at Double-Strand Breaks by Melting DNA Ends

Sharma, Sheetal; Anand, Roopesh; Zhang, Xuzhu; Francia, Sofia; Michelini, Flavia; Galbiati, Alessandro; Williams, Hannah; Ronato, Daryl A.; Masson, Jean‐Yves; Rothenberg, Eli; Ćejka, Petr; Fagagna, Fabrizio d’Adda di

doi:10.1016/j.celrep.2020.108565

Cited by 50 publications

(47 citation statements)

References 79 publications

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“…The findings indicate that downstream DDR proteins could be recruited to the breaks via these dilncRNAs and the transcription machinery, while upstream DDR factors are important for recruitment of the transcription machinery ( 142 ). More recently, a biochemical study using an in vitro transcription assay has reported that the ability of MRN to melt DNA ends, and not its nuclease activity, is important to drive dilncRNAs transcription and that the resulting transcripts seem to form transient RNA:DNA hybrids ( 143 ). However, additional work will be needed to support these findings in vivo .…”

Section: R-loops In the Dna Damage Repair Responsementioning

confidence: 99%

Untangling the crosstalk between BRCA1 and R-loops during DNA repair

Alonso

Noordermeer

2021

Nucleic Acids Research

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R-loops are RNA:DNA hybrids assembled during biological processes but are also linked to genetic instability when formed out of their natural context. Emerging evidence suggests that the repair of DNA double-strand breaks requires the formation of a transient R-loop, which eventually must be removed to guarantee a correct repair process. The multifaceted BRCA1 protein has been shown to be recruited at this specific break-induced R-loop, and it facilitates mechanisms in order to regulate R-loop removal. In this review, we discuss the different potential roles of BRCA1 in R-loop homeostasis during DNA repair and how these processes ensure faithful DSB repair.

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Section: R-loops In the Dna Damage Repair Responsementioning

confidence: 99%

Untangling the crosstalk between BRCA1 and R-loops during DNA repair

Alonso

Noordermeer

2021

Nucleic Acids Research

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“…They likely represent alternative mechanisms to clear RNA:RNA hybrids that are generated by dilncRNAs at DSB sites. DilncRNAs are transcribed from and toward DNA ends whenever RNAP II binds to break-associated MRN (Figure 3B) (Michelini et al, 2017;Sharma et al, 2021). They have important roles in the recruitment of DSB signaling factors and also serve as precursors for the Drosha and Dicer-dependent generation of DNA damage response small RNAs (DDRNAs) (Francia et al, 2012;Michelini et al, 2017;Rossiello et al, 2017;Gioia et al, 2019;Rzeszutek and Betlej, 2020).…”

Section: Rna-binding Protein-rna Interactions Are Central To Double-strand Break Signaling and Repairmentioning

confidence: 99%

New Faces of old Friends: Emerging new Roles of RNA-Binding Proteins in the DNA Double-Strand Break Response

Klaric

Wüst

Panier

2021

Front. Mol. Biosci.

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DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions. To protect genomic stability and ensure cell homeostasis, cells mount a complex signaling-based response that not only coordinates the repair of the broken DNA strand but also activates cell cycle checkpoints and, if necessary, induces cell death. The last decade has seen a flurry of studies that have identified RNA-binding proteins (RBPs) as novel regulators of the DSB response. While many of these RBPs have well-characterized roles in gene expression, it is becoming increasingly clear that they also have non-canonical functions in the DSB response that go well beyond transcription, splicing and mRNA processing. Here, we review the current understanding of how RBPs are integrated into the cellular response to DSBs and describe how these proteins directly participate in signal transduction, amplification and repair at damaged chromatin. In addition, we discuss the implications of an RBP-mediated DSB response for genome instability and age-associated diseases such as cancer and neurodegeneration.

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“…Although it has been thoroughly described that transcription is generally repressed after the appearance of DSBs ( Shanbhag et al, 2010 ; Pankotai et al, 2012 ; Kim et al, 2015 ; Manfrini et al, 2015 ), some labs have reported de novo transcription around the DSB ( Francia et al, 2012 ; Ohle et al, 2016 ; Michelini et al, 2017 ; D’Alessandro et al, 2018 ; Burger et al, 2019 ; Pessina et al, 2019 ; Vítor et al, 2019 ; Sharma et al, 2021 ). Thus, after DNA damage, RNA polymerase II is supposed to be recruited to the damaged chromatin and to start transcription around the break.…”

Section: Roles Of Different Rna Molecules In Hrmentioning

confidence: 99%

The Emerging Role of RNA Modifications in DNA Double-Strand Break Repair

Jimeno

Balestra

Huertas

2021

Front. Mol. Biosci.

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The correct repair of DNA double-strand breaks is essential for maintaining the stability of the genome, thus ensuring the survival and fitness of any living organism. Indeed, the repair of these lesions is a complicated affair, in which several pathways compete for the DNA ends in a complex balance. Thus, the fine-tuning of the DNA double-strand break repair pathway choice relies on the different regulatory layers that respond to environmental cues. Among those different tiers of regulation, RNA modifications have just emerged as a promising field.

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MRE11-RAD50-NBS1 Complex Is Sufficient to Promote Transcription by RNA Polymerase II at Double-Strand Breaks by Melting DNA Ends

Cited by 50 publications

References 79 publications

Untangling the crosstalk between BRCA1 and R-loops during DNA repair

Untangling the crosstalk between BRCA1 and R-loops during DNA repair

New Faces of old Friends: Emerging new Roles of RNA-Binding Proteins in the DNA Double-Strand Break Response

The Emerging Role of RNA Modifications in DNA Double-Strand Break Repair

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