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      Regulatory and Functional Involvement of Long Non-Coding RNAs in DNA Double-Strand Break Repair Mechanisms

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          Abstract

          Protection of genome integrity is vital for all living organisms, particularly when DNA double-strand breaks (DSBs) occur. Eukaryotes have developed two main pathways, namely Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR), to repair DSBs. While most of the current research is focused on the role of key protein players in the functional regulation of DSB repair pathways, accumulating evidence has uncovered a novel class of regulating factors termed non-coding RNAs. Non-coding RNAs have been found to hold a pivotal role in the activation of DSB repair mechanisms, thereby safeguarding genomic stability. In particular, long non-coding RNAs (lncRNAs) have begun to emerge as new players with vast therapeutic potential. This review summarizes important advances in the field of lncRNAs, including characterization of recently identified lncRNAs, and their implication in DSB repair pathways in the context of tumorigenesis.

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          Most cited references76

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          The transcriptional landscape of the mammalian genome.

          P Carninci, T Kasukawa, S. Katayama … (2005)
          This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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            Gene regulation by long non-coding RNAs and its biological functions

            Luisa Statello, Chun-Jie Guo, Ling-Ling Chen … (2020)
            Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA and proteins, lncRNAs can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic mRNAs and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that lncRNAs are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.
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              The DNA-damage response in human biology and disease.

              Jiri Bartek, Stephen P. Jackson (2009)
              The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.
              Article 0 comments Cited 922 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Francesca Storici: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Cells
                Journal ID (iso-abbrev): Cells
                Journal ID (publisher-id): cells
                Title: Cells
                Publisher: MDPI
                ISSN (Electronic): 2073-4409
                Publication date (Electronic): 15 June 2021
                Publication date Collection: June 2021
                Volume: 10
                Issue: 6
                Electronic Location Identifier: 1506
                Affiliations
                [1 ]Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National Kapodistrian University of Athens (NKUA), 75 Mikras Asias Str., Goudi, GR-11527 Athens, Greece; a.papaspyropoulos@ 123456med.uoa.gr (A.P.); nlagopati@ 123456med.uoa.gr (N.L.); ioanna.mourkioti@ 123456gmail.com (I.M.); andriani.an22@ 123456hotmail.com (A.A.); spkyriaz@ 123456gmail.com (S.K.); mliontos@ 123456gmail.com (M.L.)
                [2 ]Biomedical Research Foundation, Academy of Athens, GR-11527 Athens, Greece
                [3 ]Oncology Unit, Department of Clinical Therapeutics, Medical School, National and Kapodistrian University of Athens, Alexandra Hospital, GR-11528 Athens, Greece
                [4 ]Molecular and Clinical Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M20 4GJ, UK
                [5 ]Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, GR-11527 Athens, Greece
                Author notes
                [* ]Correspondence: vgorg@ 123456med.uoa.gr (V.G.); akotsin@ 123456med.uoa.gr (A.K.); Tel.: +30-210-746-2352 (V.G.); +30-210-746-2420 (A.K.)
                [†]

                These authors contributed equally.

                Author information
                https://orcid.org/0000-0001-7192-4575
                https://orcid.org/0000-0001-9001-4112
                Article
                Publisher ID: cells-10-01506
                DOI: 10.3390/cells10061506
                PMC ID: 8232683
                PubMed ID: 34203749
                SO-VID: 755f90db-d8ae-4ec8-b060-588a041c4ad4
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 25 April 2021
                Date accepted : 10 June 2021
                Categories
                Subject: Review

                Keywords: long non-coding rnas,double-strand breaks (dsb),dna damage response and repair (ddrr),tumorigenesis
                Data availability:
                Keywords: long non-coding rnas, double-strand breaks (dsb), dna damage response and repair (ddrr), tumorigenesis

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