 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 22, 2023 |
| Title |
Delineation of two multi-invasion-induced rearrangement pathways that differently affect genome stability |
| Organism |
Saccharomyces cerevisiae |
| Experiment type |
Other
|
| Summary |
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.
|
| |
|
| Overall design |
DNA from APY85 and APY89 parental strains (Lys-) and of APY85 and APY89 Lys+ recombinants obtained following DSB formation on chr. V was isolated, sequenced and/or analyzed by aCGH to identify structural variants and copy number variations.
|
| |
|
| Contributor(s) |
Piazza A, Watson RA |
| Citation(s) |
37541760 |
| BioProject |
PRJNA967211 |
| |
| Submission date |
May 17, 2023 |
| Last update date |
Nov 22, 2023 |
| Contact name |
Aurele Piazza |
| E-mail(s) |
aurele.piazza@ens-lyon.fr
|
| Organization name |
ENS Lyon
|
| Street address |
46 Allee d'Italie
|
| City |
Lyon |
| ZIP/Postal code |
69007 |
| Country |
France |
| |
|
| Platforms (1) |
| GPL17143 |
Illumina MiSeq (Saccharomyces cerevisiae) |
|
| Samples (24)
|
|
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232732_RAW.tar |
20.4 Mb |
(http)(custom) |
TAR (of BEDGRAPH, CLC) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...