RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination

Liu, Sijie; Yu, Hua-Zhong; Wang, Jingna; Li, Lingyan; Yuan, Junjie; Zhang, Bo; Wang, Ziyang; Ji, Jianguo; Kong, Delong

doi:10.1016/j.cell.2021.01.048

Cited by 91 publications

(102 citation statements)

References 56 publications

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“…These noncoding RNAs promote the DSB response by helping to recruit DSB signaling and repair factors to chromatin, either directly through RNA-protein interactions or indirectly by contributing to phase separation locally around the break site. In addition, they can assist repair by temporarily stabilizing the DSB ends, protecting the 3′ ssDNA overhangs from nucleases during end resection, modulating DNA-protein interactions and protein activities, by serving as repair templates and by regulating local chromatin remodeling (Storici et al, 2007;Shen et al, 2011;Wei et al, 2012Wei et al, , 2015Sharma and Misteli, 2013;D' Adda di Fagagna, 2014;Keskin et al, 2014;Yang and Qi, 2015;Chakraborty et al, 2016;Thapar, 2018;Durut and Mittelsten Scheid, 2019;Bader et al, 2020;Ketley and Gullerova, 2020;Liu et al, 2021).…”

Section: Rna-binding Protein-rna Interactions Are Central To Double-smentioning

confidence: 99%

“…Like RNAP II, RNA Polymerase III (RNAP III) is also recruited to DSBs in a MRN-dependent manner (Liu et al, 2021). After MRN and CtIP begin end-resection, RNAP III uses the resulting ssDNA region to synthesize RNA and displace the 5′ strand, which generates a RNA:DNA hybrid.…”

Section: Rna-binding Protein-rna Interactions Are Central To Double-smentioning

confidence: 99%

“…These RNA:DNA hybrids likely promote HR by preventing the 3′ ssDNA overhang that is essential for RAD51-mediated strand exchange from being degraded during end-resection. Accordingly, depletion of RNAP III in mammalian cells hinders DNA end-resection and HR-directed repair (Liu et al, 2021). It is unclear which proteins resolve RNA:DNA hybrids produced by RNAPIII, but it is possible that SETX, XRN2, EXOSC10, RNase H2, and/or DDX1 are involved in their processing since all of these RBPs promote HR-mediated DSB repair (Marin-Vicente et al, 2015;Li et al, 2016;Cohen et al, 2018;D'Alessandro et al, 2018;Dang and Morales, 2020).…”

Section: Rna-binding Protein-rna Interactions Are Central To Double-smentioning

confidence: 99%

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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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Section: Rna-binding Protein-rna Interactions Are Central To Double-smentioning

confidence: 99%

Section: Rna-binding Protein-rna Interactions Are Central To Double-smentioning

confidence: 99%

Section: Rna-binding Protein-rna Interactions Are Central To Double-smentioning

confidence: 99%

See 1 more Smart Citation

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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“…Resection of 5 ends is started by MRN complex (MRE11, RAD50, NBS1 proteins), which is activated by CtIP tetramer (RBBP8), and then the resection is extended by EXO1 and BLM-DNA2 proteins (Figure 4) [110]. Recently, RNA polymerase III was shown to protect 3 overhangs by forming RNA-DNA hybrids [111]. RPA is displaced by BRCA2 and BRCA1-BARD1 with the help of PALB2, and 3 end invasion is facilitated by RAD52 (Figure 4) [112,113].…”

Section: All Pathways Of Homology-directed Repair Are Controlled By Rnasmentioning

confidence: 99%

The Role of RNA in DNA Breaks, Repair and Chromosomal Rearrangements

et al. 2021

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Incorrect reparation of DNA double-strand breaks (DSB) leading to chromosomal rearrangements is one of oncogenesis’s primary causes. Recently published data elucidate the key role of various types of RNA in DSB formation, recognition and repair. With growing interest in RNA biology, increasing RNAs are classified as crucial at the different stages of the main pathways of DSB repair in eukaryotic cells: nonhomologous end joining (NHEJ) and homology-directed repair (HDR). Gene mutations or variation in expression levels of such RNAs can lead to local DNA repair defects, increasing the chromosome aberration frequency. Moreover, it was demonstrated that some RNAs could stimulate long-range chromosomal rearrangements. In this review, we discuss recent evidence demonstrating the role of various RNAs in DSB formation and repair. We also consider how RNA may mediate certain chromosomal rearrangements in a sequence-specific manner.

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“…Nascent hybrids are involved in both C-NHEJ and HR and could act as a homologous template for DNA repair. Nonetheless, persistent hybrids have negative consequences on the repair of transcribed genes [86,87], and may lead to replicative stress.…”

Section: Rna-dna Hybridsmentioning

confidence: 99%

A Link between Replicative Stress, Lamin Proteins, and Inflammation

Willaume

Rass

Fontanilla-Ramirez

et al. 2021

Genes

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Double-stranded breaks (DSB), the most toxic DNA lesions, are either a consequence of cellular metabolism, programmed as in during V(D)J recombination, or induced by anti-tumoral therapies or accidental genotoxic exposure. One origin of DSB sources is replicative stress, a major source of genome instability, especially when the integrity of the replication forks is not properly guaranteed. To complete stalled replication, restarting the fork requires complex molecular mechanisms, such as protection, remodeling, and processing. Recently, a link has been made between DNA damage accumulation and inflammation. Indeed, defects in DNA repair or in replication can lead to the release of DNA fragments in the cytosol. The recognition of this self-DNA by DNA sensors leads to the production of inflammatory factors. This beneficial response activating an innate immune response and destruction of cells bearing DNA damage may be considered as a novel part of DNA damage response. However, upon accumulation of DNA damage, a chronic inflammatory cellular microenvironment may lead to inflammatory pathologies, aging, and progression of tumor cells. Progress in understanding the molecular mechanisms of DNA damage repair, replication stress, and cytosolic DNA production would allow to propose new therapeutical strategies against cancer or inflammatory diseases associated with aging. In this review, we describe the mechanisms involved in DSB repair, the replicative stress management, and its consequences. We also focus on new emerging links between key components of the nuclear envelope, the lamins, and DNA repair, management of replicative stress, and inflammation.

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RNA polymerase III is required for the repair of DNA double-strand breaks by homologous recombination

Cited by 91 publications

References 56 publications

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

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

The Role of RNA in DNA Breaks, Repair and Chromosomal Rearrangements

A Link between Replicative Stress, Lamin Proteins, and Inflammation

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