DNA lesions can frequently precede DNA:RNA hybrid accumulation [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1104632 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28807961_1.fastq.gz | Fastqsanger.gz | |||
| SRR28807961_2.fastq.gz | Fastqsanger.gz | |||
| SRR28807962_1.fastq.gz | Fastqsanger.gz | |||
| SRR28807962_2.fastq.gz | Fastqsanger.gz | |||
| SRR28807963_1.fastq.gz | Fastqsanger.gz |
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Project description:DNA lesions can frequently precede DNA:RNA hybrid accumulation [DRIP-seq]
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Project description:While DNA:RNA hybrids contribute to multiple genomic transactions, their unscheduled formation is a recognized source of DNA lesions. Here, through a suite of systematic screens, we rather observed that a wide range of yeast mutant situations primarily triggering DNA damage actually leads to hybrid accumulation. Focusing on Okazaki fragment processing, we established that genic hybrids can actually form as a consequence of replication-born discontinuities such as unprocessed flaps or unligated Okazaki fragments. Strikingly, such “post-lesion” DNA:RNA hybrids neither detectably contribute to genetic instability, nor disturb gene expression, as opposed to “pre-lesion” hybrids formed upon defective mRNA biogenesis, e.g., THO complex mutants. Post-lesion hybrids similarly arise in distinct genomic instability situations, triggered by pharmacological or genetic manipulation of DNA-dependent processes, both in yeast and human cells. Altogether, our data establish that the accumulation of transcription-born DNA:RNA hybrids can occur as a consequence of various types of natural or pathological DNA lesions, yet do not necessarily aggravate their genotoxicity.
2025-02-06 | GSE265892 | GEO
Project description:While DNA:RNA hybrids contribute to multiple genomic transactions, their unscheduled formation is a recognized source of DNA lesions. Here, through a suite of systematic screens, we rather observed that a wide range of yeast mutant situations primarily triggering DNA damage actually leads to hybrid accumulation. Focusing on Okazaki fragment processing, we established that genic hybrids can actually form as a consequence of replication-born discontinuities such as unprocessed flaps or unligated Okazaki fragments. Strikingly, such “post-lesion” DNA:RNA hybrids neither detectably contribute to genetic instability, nor disturb gene expression, as opposed to “pre-lesion” hybrids formed upon defective mRNA biogenesis, e.g., THO complex mutants. Post-lesion hybrids similarly arise in distinct genomic instability situations, triggered by pharmacological or genetic manipulation of DNA-dependent processes, both in yeast and human cells. Altogether, our data establish that the accumulation of transcription-born DNA:RNA hybrids can occur as a consequence of various types of natural or pathological DNA lesions, yet do not necessarily aggravate their genotoxicity.
2025-02-06 | GSE265894 | GEO
Project description:Longitudinal DNA methylation differences precede type 1 diabetes
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Project description:DNA repair and autophagy are distinct biological processes vital for cell survival. Although autophagy helpsmaintain genome stability, there is no evidence of its direct role in the repair of DNA lesions. We discoveredthat lysosomes process topoisomerase 1 cleavage complexes (TOP1cc) DNA lesions in vertebrates. Selectivedegradation of TOP1cc by autophagy directs DNA damage repair and cell survival at clinically relevantdoses of topoisomerase 1 inhibitors. TOP1cc are exported from the nucleus to lysosomes through a transientalteration of the nuclear envelope and independent of the proteasome. Mechanistically, the autophagy receptorTEX264 acts as a TOP1cc sensor at DNA replication forks, triggering TOP1cc processing by theQ8 p97 ATPase and mediating the delivery of TOP1cc to lysosomes in an MRE11-nuclease- and ATR-kinasedependentmanner. We found an evolutionarily conserved role for selective autophagy in DNA repair that enQ2ables cell survival, protects genome stability, and is clinically relevant for colorectal cancer patients.
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Project description:BACKGROUND Autofluorescence bronchoscopy (AFB) is a valid strategy for detecting premalignant endobronchial lesions. However, no biomarker can reliably predict lung cancer risk of subjects with AFB-visualized premalignant lesions. Our present study was set out to identify AFB-visualized squamous metaplastic lesions with malignant potential by DNA copy number profiling. METHODS Regular AFB-examinations in 474 subjects at risk of lung cancer identified 6 subjects with SqM lesions at baseline and carcinoma (in situ) at the initial SqM site at follow-up bronchoscopy. These progressive SqM lesions were compared for immunostaining pattern and arrayCGH-based chromosomal profiles to 23 SqM of subjects who remained cancer-free. Specific copy number alterations (CNAs) linked to cancer risk were identified and accuracy of CNAs to predict endobronchial cancer in this series was determined. RESULTS At baseline, p53, p63 and Ki-67 immunostaining were not predictive for a differential clinical outcome of SqM lesions. The mean number of CNAs in baseline SqM of cases was significantly higher compared to controls (p<0.01). Chromosomal regions significantly more frequently altered in SqM of cases were 3p26.3-p11.1, 3q26.2-q29, 9p13.3-p13.2, and 17p13.3-p11.2 (FWER<0.10). CNAs were specifically detected at the site of future cancer. In cases, baseline-detected CNAs persisted in subsequent biopsies taken from the initial site, and levels increased towards cancer progression. CNAs at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3, predicted cancer risk for AFB-visualized SqM with 97% accuracy. CONCLUSION Our data strongly suggest that the presence of specific DNA copy number alterations in endobronchial SqM lesions predict endobronchial cancer.
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Project description:DNA methylation profiling of gastric cancer and precursor lesions
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Project description:Protecting the integrity of their genome is critical to all species. The surveillance and maintenance of the genome of every organism is orchestrated by a highly regulated combination of DNA damage response and specific DNA repair pathways. Two of these critical pathways are base excision repair (BER) and ribonucleotide excision repair (RER). Here, we investigate the phylogenetic diversity in the recognition and repair of three well-established DNA lesions, primarily repaired by BER or RER: 1) 8-oxoguanine, 2) an abasic site, and 3) incorporated ribonucleotide in DNA in E. coli, B. subtilis, H. salinarum, T. brucei, T. thermophila, S. cerevisiae, S. pombe, C. elegans, human HeLa and HEK293 cells, A. thaliana, and Z. mays. Using quantitative mass spectrometry, we identified 337 enriched interactors across these species. Of these proteins, 140 were previously characterized to be involved in DNA repair, and 39 proteins were newly identified due to their homology to previously studied repair proteins. For 10 of the 11 species, we identify unique, uncharacterized proteins that lack homology to any protein within the included 11 species. Our study emphasizes strong crosstalk between RER and BER and highlights the evolutionary conservation of this cross recognition across all domains of life.
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