Delineation of two multi-invasion-induced rearrangement pathways that differently affect genome stability
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA975123 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Punctuated bursts of structural genomic variations (SVs) have been described in various organisms, but their etiology remains incompletely understood. Homologous recombination (HR) is a template-guided mechanism of repair of DNA double-strand breaks and stalled or collapsed replication forks. We recently identified a DNA break amplification and genome rearrangement pathway originating from the endonucleolytic processing of a multi-invasion (MI) DNA joint molecule formed during HR. Genome-wide sequencing approaches confirmed that multi-invasioninduced rearrangement (MIR) frequently leads to several repeat-mediated SVs and aneuploidies. Using molecular and genetic analysis, and a novel, highly sensitive proximity ligation-based assay for chromosomal rearrangement quantification, we further delineate two MIR sub-pathways. MIR1 is a universal pathway occurring in any sequence context, which generates secondary breaks and frequently leads to additional SVs. MIR2 occurs only if recombining donors exhibit substantial homology, and results in sequence insertion without additional break or SV. The most detrimental MIR1 pathway occurs late on a subset of persisting DNA joint molecules in a PCNA/Polδ- independent manner, unlike recombinational DNA synthesis. This work provides a refined mechanistic understanding of these HR-based SV formation pathways and shows that complex repeat-mediated SVs can occur without displacement DNA synthesis. Sequence signatures for inferring MIR1 from long-read data are proposed.
2023-08-22 | GSE233144 | GEO
Project description:Punctuated bursts of structural genomic variations (SVs) have been described in various organisms, but their etiology remains incompletely understood. Homologous recombination (HR) is a template-guided mechanism of repair of DNA double-strand breaks and stalled or collapsed replication forks. We recently identified a DNA break amplification and genome rearrangement pathway originating from the endonucleolytic processing of a multi-invasion (MI) DNA joint molecule formed during HR. Genome-wide sequencing approaches confirmed that multi-invasion-induced rearrangement (MIR) frequently leads to several repeat-mediated SVs and aneuploidies. Using molecular and genetic analysis, and a novel, highly sensitive proximity ligation-based assay for chromosomal rearrangement quantification, we further delineate two MIR sub-pathways. MIR1 is a universal pathway occurring in any sequence context, which generates secondary breaks and frequently leads to additional SVs. MIR2 occurs only if recombining donors exhibit substantial homology, and results in sequence insertion without additional break or SV. The most detrimental MIR1 pathway occurs late on a subset of persisting DNA joint molecules in a PCNA/Pold-independent manner, unlike recombinational DNA synthesis. This work provides a refined mechanistic understanding of these HR-based SV formation pathways and shows that complex repeat-mediated SVs can occur without displacement DNA synthesis. Sequence signatures for inferring MIR1 from long-read data are proposed.
2023-08-22 | GSE232732 | GEO
Project description:Punctuated bursts of structural genomic variations (SVs) have been described in various organisms, but their etiology remains incompletely understood. Homologous recombination (HR) is a template-guided mechanism of repair of DNA double-strand breaks and stalled or collapsed replication forks. We recently identified a DNA break amplification and genome rearrangement pathway originating from the endonucleolytic processing of a multi-invasion (MI) DNA joint molecule formed during HR. Genome-wide approaches confirmed that multi-invasion-induced rearrangement (MIR) frequently leads to several repeat-mediated SVs and aneuploidies. Using molecular and genetic analysis and a novel, highly sensitive proximity ligation-based assay for chromosomal rearrangement quantification, we further delineate two MIR subpathways. MIR1 is a universal pathway occurring in any sequence context, which generates secondary breaks and frequently leads to additional SVs. MIR2 occurs only if recombining donors exhibit substantial homology and results in sequence insertion without additional breaks or SVs. The most detrimental MIR1 pathway occurs late on a subset of persisting DNA joint molecules in a PCNA/Polδ-independent manner, unlike recombinational DNA synthesis. This work provides a refined mechanistic understanding of these HR-based SV formation pathways and shows that complex repeat-mediated SVs can occur without displacement DNA synthesis. Sequence signatures for inferring MIR1 from long-read data are proposed.
| S-EPMC10499017 | biostudies-literature
Project description:Delineation of two multi-invasion-induced rearrangement pathways that differently affect genome stability
| PRJNA967211 | ENA
Project description:Differently treated alfalfa silages affect the in vitro ruminal microbiota composition
| PRJEB32442 | ENA
Project description:Circular RNAs affect mRNA stability
| PRJNA1002274 | ENA
Project description:SUMO protease and proteasome recruitment at the nuclear periphery differently affect replication dynamics at arrested forks.
| PRJNA1037365 | ENA
Project description:Chloroplast DNA rearrangement assay
| PRJEB41149 | ENA
Project description:The vestibular system is critical for human locomotion. Any deteriorated vestibular system leads to gait instability. In the past decades, these alternations in gait patterns have been majorly measured by the spatial-temporal gait parameters and respective variabilities. However, measuring gait characteristics cannot capture the full aspect of motor controls. Thus, to further understand the effects of deteriorated vestibular system on gait performance, additional measurement needs to be taken into consideration. This study proposed using the margin of stability (MOS) to identify the patterns of dynamic control under different types of mastoid vibrations in walking. This study hypothesized that (1) using the MOS method could facilitate the understanding of another aspect of motor control induced by different types of mastoid vibrations, and (2) applying the mastoid vibrations could induce the asymmetric MOS. Twenty healthy young adults were recruited. Two electromechanical vibrotactile transducers were placed on the bilateral mastoid process to apply different types of vestibular vibrations (bilateral, unilateral, and no vibration). A motion capture system with eight cameras was used to measure the MOSap (margin of stability in the anterior-posterior direction), MOSml (margin of stability in the medial-lateral direction), and respective variabilities. The results were in line with the hypotheses that both bilateral and unilateral mastoid vibrations significantly increased MOSap (p = 0.036, p < 0.001), MOSml (p = 0.012, p < 0.001), and respective variabilities p = 0.001, p < 0.001; p = 0.001, p < 0.01 when compared to the no vibration condition. Also, significantly larger MOSml (p = 0.001), MOSml variability (p < 0.023), MOSap (p < 0.001), and MOSap variability (p = 0.002) were observed under the unilateral vibration condition than that observed under the bilateral vibration condition. The above-mentioned result found that different types of mastoid vibrations affected the MOS differently, suggesting different patterns of control mechanisms under different sensory-conflicted situations. Besides, a significant difference between the dominant and non-dominant legs was observed in MOSml. Moreover, applying the unilateral mastoid vibrations induced a greater symmetric index of MOSml, suggesting that more active control in balance was needed in the medial-lateral than in the anterior-posterior direction.
| S-EPMC9271872 | biostudies-literature
Project description:High-throughput capture of cis-rearrangement and trans-rearrangement sequence [LAM-HTGTS]
| PRJNA574913 | ENA