Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs

Thapar, Roopa

doi:10.20944/preprints201810.0500.v1

Cited by 17 publications

(19 citation statements)

References 117 publications

(137 reference statements)

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“…It is emerging that RNA has many functions in the repair of DSBs [ 11–14 ]. RNA can be either coding messenger RNA (mRNA), translated into proteins, or non-coding RNA (ncRNA), not translated into protein.…”

Section: Rna In Dsb Repairmentioning

confidence: 99%

“…MiRNAs can down-regulate the expression of mRNAs in a process known as RNA interference (RNAi) by guiding RISC to an mRNA with sequence complementarity. mRNA degradation machinery can then be recruited which either disrupts the translational machinery or degrades the target mRNA [ 11 , 19 ].…”

Section: Mirna Roles In Dsb Repairmentioning

confidence: 99%

“…Over 60% of protein-coding mRNAs are predicted to be targeted by miRNAs [ 20 ], and one miRNA can target many different genes [ 29 ]. Of these miRNAs, many are now known to play key roles in DSB repair, regulating the levels of a variety of DSB repair factors to augment the DDR to DSBs ( Table 1 ) [ 11 ]. Examples of miRNAs regulating DSB repair factors include miR-421, miR-100, and miR-181 regulation of ATM [ 20 , 28 ], miR-24 and miR-138 regulation of H2AX [ 28 , 30 ], and miR-34 family regulation of RAD51 [ 31 ].…”

Section: Mirna Roles In Dsb Repairmentioning

confidence: 99%

“…The expression of various lncRNAs can be modulated in response to IR [ 67 , 68 ]. LncRNAs also bind DSB repair factors, of which examples include MALAT1, TERRA, and lincRNA-p21 lncRNAs (reviewed in [ 11 ]). In this section we will focus on a handful of specific examples of lncRNAs which have recently been implicated in the DDR, both directly, such as through binding to DNA repair proteins, and indirectly, such as by regulating translation of proteins involved in genome stability and DNA repair, highlighting the variety of mechanisms by which lncRNAs can influence repair ( Figure 2 ).…”

Section: Lncrnas: Direct and Indirect Regulators Of Dsb Repairmentioning

confidence: 99%

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Jack of all trades? The versatility of RNA in DNA double-strand break repair

Ketley

Gullerová

2020

Essays in Biochemistry

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Abstract The mechanisms by which RNA acts in the DNA damage response (DDR), specifically in the repair of DNA double-strand breaks (DSBs), are emerging as multifaceted and complex. Different RNA species, including but not limited to; microRNA (miRNA), long non-coding RNA (lncRNA), RNA:DNA hybrid structures, the recently identified damage-induced lncRNA (dilncRNA), damage-responsive transcripts (DARTs), and DNA damage-dependent small RNAs (DDRNAs), have been shown to play integral roles in the DSB response. The diverse properties of these RNAs, such as sequence, structure, and binding partners, enable them to fulfil a variety of functions in different cellular contexts. Additionally, RNA can be modified post-transcriptionally, a process which is regulated in response to cellular stressors such as DNA damage. Many of these mechanisms are not yet understood and the literature contradictory, reflecting the complexity and expansive nature of the roles of RNA in the DDR. However, it is clear that RNA is pivotal in ensuring the maintenance of genome integrity. In this review, we will discuss and summarise recent evidence which highlights the roles of these various RNAs in preserving genomic integrity, with a particular focus on the emerging role of RNA in the DSB repair response.

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Section: Rna In Dsb Repairmentioning

confidence: 99%

Section: Mirna Roles In Dsb Repairmentioning

confidence: 99%

Section: Mirna Roles In Dsb Repairmentioning

confidence: 99%

Section: Lncrnas: Direct and Indirect Regulators Of Dsb Repairmentioning

confidence: 99%

See 2 more Smart Citations

Jack of all trades? The versatility of RNA in DNA double-strand break repair

Ketley

Gullerová

2020

Essays in Biochemistry

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“…In the past few decades, understanding of cellular signaling for DSBs repair has been gradually uncovered [11,12]. Also, implication of non-coding RNAs (ncRNAs) in this process has been the focus on cancer research [13,14].…”

Section: Introductionmentioning

confidence: 99%

LINC01094 triggers radio-resistance in clear cell renal cell carcinoma via miR-577/CHEK2/FOXM1 axis

Jiang

Yang

et al. 2020

Cancer Cell Int

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Background: Radioresistance is an obstacle to limit efficacy of radiotherapy. Meanwhile, long non-coding RNAs (lncRNAs) have been reported to affect radioresistance. Here, we aimed to investigate lncRNAs involving radioresistance development of clear cell renal cell carcinoma (ccRCC), the most frequent type of renal cell carcinoma (RCC). Methods: The mRNA and protein expressions of genes were measured via qRT-PCR and western blot. The relationships among genes were verified by RIP and luciferase reporter assay. The radioresistance of ccRCC cells was evaluated through clonogenic survival assay, MTT assay and TUNEL assay. Results: LINC01094 was over-expressed in ccRCC cell lines. LINC01094 expression was increased along with the radiation exposure time and the final stable level was 8 times of the initial level. Knockdown of LINC01094 resulted in enhanced radiosensitivity of ccRCC cells. Mechanically, LINC01094 was a ceRNA of CHEK2 by sponging miR-577. Also, the enhancement of LINC01094 on ccRCC radioresistance was mediated by CHEK2-stabilized FOXM1 protein. Conclusion: LINC01094 facilitates ccRCC radioresistance by targeting miR-577/CHEK2/FOXM1 axis, blazing a new trail for overcoming radioresistance in ccRCC.

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The RNA‐binding protein La/SSB associates with radiation‐induced DNA double‐strand breaks in lung cancer cell lines

Staudacher

Liapis

et al. 2021

Cancer Reports

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Background Platinum‐based chemotherapy and radiotherapy are standard treatments for non‐small cell lung cancer, which is the commonest, most lethal cancer worldwide. As a marker of treatment‐induced cancer cell death, we have developed a radiodiagnostic imaging antibody, which binds to La/SSB. La/SSB is an essential, ubiquitous ribonuclear protein, which is over expressed in cancer and plays a role in resistance to cancer therapies. Aim In this study, we examined radiation‐induced DNA double strand breaks (DSB) in lung cancer cell lines and examined whether La/SSB associated with these DSB. Method Three lung cancer lines (A549, H460 and LL2) were irradiated with different X‐ray doses or X‐radiated with a 5 Gy dose and examined at different time‐points post‐irradiation for DNA DSB in the form of γ‐H2AX and Rad51 foci. Using fluorescence microscopy, we examined whether La/SSB and γ‐H2AX co‐localise and performed proximity ligation assay (PLA) and co‐immunoprecipitation to confirm the interaction of these proteins. Results We found that the radio‐resistant A549 cell line compared to the radio‐sensitive H460 cell line showed faster resolution of radiation‐induced γ‐H2AX foci over time. Conversely, we found more co‐localised γ‐H2AX and La/SSB foci by PLA in irradiated A549 cells. Conclusion The co‐localisation of La/SSB with radiation‐induced DNA breaks suggests a role of La/SSB in DNA repair, however further experimentation is required to validate this.

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Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs

Cited by 17 publications

References 117 publications

Jack of all trades? The versatility of RNA in DNA double-strand break repair

Jack of all trades? The versatility of RNA in DNA double-strand break repair

LINC01094 triggers radio-resistance in clear cell renal cell carcinoma via miR-577/CHEK2/FOXM1 axis

The RNA‐binding protein La/SSB associates with radiation‐induced DNA double‐strand breaks in lung cancer cell lines

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