Hypothesis: transcript‐templated repair of DNA double‐strand breaks

Trott, Deborah A.; Porter, Andrew C.G.

doi:10.1002/bies.20339

Cited by 14 publications

(6 citation statements)

References 40 publications

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“…It was hypothesized that RNA transcripts could provide an alternative template for accurate repair [33]. Studies by Xu et al also proposed the involvement of RNA templated HR to explain the high frequency of homozygosity in rice [34].…”

Section: Rna On the Frontlines Of Dna Damagementioning

confidence: 99%

DNA repair by RNA: Templated, or not templated, that is the question

2016

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Cells are continuously exposed to both endogenous and exogenous sources of genomic stress. To maintain chromosome stability, a variety of mechanisms have evolved to cope with the multitude of genetic abnormalities that can arise over the life of a cell. Still, failures to repair these lesions are the driving force of cancers and other degenerative disorders. DNA double-strand breaks (DSBs) are among the most toxic genetic lesions, inhibiting cell ability to replicate, and are sites of mutations and chromosomal rearrangements. DSB repair is known to proceed via two major mechanisms: homologous recombination (HR) and non-homologous end joining (NHEJ). HR reliance on the exchange of genetic information between two identical or nearly identical DNA molecules offers increased accuracy. While the preferred substrate for HR in mitotic cells is the sister chromatid, this is limited to the S and G2 phases of the cell cycle. However, abundant amounts of homologous genetic substrate may exist throughout the cell cycle in the form of RNA. Considered an uncommon occurrence, the direct transfer of information from RNA to DNA is thought to be limited to special circumstances. Studies have shown that RNA molecules reverse transcribed into cDNA can be incorporated into DNA at DSB sites via a non-templated mechanism by NHEJ or a templated mechanism by HR. In addition, synthetic RNA molecules can directly template the repair of DSBs in yeast and human cells via an HR mechanism. New work suggests that even endogenous transcript RNA can serve as a homologous template to repair a DSB in chromosomal DNA. In this perspective, we will review and discuss the recent advancements in DSB repair by RNA via non-templated and templated mechanisms. We will provide current findings, models and future challenges investigating RNA and its role in DSB repair.

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Section: Rna On the Frontlines Of Dna Damagementioning

confidence: 99%

DNA repair by RNA: Templated, or not templated, that is the question

2016

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“…16 Transcript-templated repair of DNA double-strand breaks is possible when RNA transcripts are used as templates for HDR. 17 The advances in sequencing technology and the Encyclopedia of DNA Elements (ENCODE) highlighted the "dark matter of genome" non-coding transcripts (ncRNAs: miRNAs, piRNAs, siRNAs ) in funding of the new functional regulatory regions. 18 Bioinformatics allows to detect transposable elements transcripts from RNA-seq data for characterization of novel insertions from DNA-seq data from the Cancer Genome Atlas (TCGA) what matched normal and primary tumor samples.…”

Section: Resultsmentioning

confidence: 99%

"Dark matter of genome” in cancer

Lushnikova¹

2019

JCPCR

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Cancer is a complex disease involved defects in hundreds of genes and multiple errors in cell intra-and extracellular networks. There are more than 100 types of tumors. Every type of cells in every tissue of the body may be changed to abnormal cell growth. What is the actual trigger for cancer? Genetic alterations in tumor suppressor genes, mutations or amplifications in oncogene genes (and MYC-containing dmin) can influence on metabolic pathways, proteome imbalances and cause the development of neoplasms. 1-6 Defective DNA replication can result in genomic instability as DNA alterations, chromosomal rearrangements, aneuploidy, and gene amplifications which associated with tumors. 7 Chromosomal instability (CIN) is subtype of genomic instability that cause the defects in chromosomal organization and segregation. 8 How "junk" DNA may be functionally involved in tumorigenesis?

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“…Early work demonstrated that RNA could play an indirect role in genome modification and DSB repair if converted into a DNA copy (cDNA) and stitched into damaged sites via NHEJ in yeast and mammalian cells. − Not only can these cDNA molecules be inserted in a nonhomologous manner at sites of DSBs, but cDNA can also function as a homologous donor template to accurately repair DSBs via homologous recombination (HR) in budding yeast . However, can an RNA molecule serve directly as a template for repairing/modifying DNA without the need of being converted into cDNA? , Indeed, RNA-containing DNA oligonucleotides can serve as templates for gene editing on plasmid or chromosomal DNA in Escherichia coli. − Similarly, RNA-containing and RNA-only oligonucleotides can serve as RNA donor templates for DSB repair, a phenomenon observed in yeast and human cells. , In addition, artificial long RNA templates injected in ciliate cells can guide genomic rearrangements (see section for details).…”

Section: Rna-templated Dna Repair In Yeast and Mammalsmentioning

confidence: 99%

From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond

et al. 2018

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Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

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Hypothesis: transcript‐templated repair of DNA double‐strand breaks

Cited by 14 publications

References 40 publications

DNA repair by RNA: Templated, or not templated, that is the question

DNA repair by RNA: Templated, or not templated, that is the question

"Dark matter of genome” in cancer

From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond

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