Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells
Abstract Recent studies revealed classes of recurrent DNA double-strand breaks (DSBs) in neural stem/progenitor cells, including transcription-associated, promoter-proximal breaks and recurrent DSB clusters in late-replicating, long neural genes that may give rise to somatic brain mosaicism. The mec...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-17452-0 |
| _version_ | 1811315132153724928 |
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| author | Supawat Thongthip Annika Carlson Magdalena P. Crossley Bjoern Schwer |
| author_facet | Supawat Thongthip Annika Carlson Magdalena P. Crossley Bjoern Schwer |
| author_sort | Supawat Thongthip |
| collection | DOAJ |
| description | Abstract Recent studies revealed classes of recurrent DNA double-strand breaks (DSBs) in neural stem/progenitor cells, including transcription-associated, promoter-proximal breaks and recurrent DSB clusters in late-replicating, long neural genes that may give rise to somatic brain mosaicism. The mechanistic factors promoting these different classes of DSBs in neural stem/progenitor cells are not understood. Here, we elucidated the genome-wide landscape of RNA:DNA hybrid structures called “R-loops” in primary neural stem/progenitor cells undergoing aphidicolin-induced, mild replication stress to assess the potential contribution of R-loops to the different, recurrent classes of DNA break “hotspots”. We find that R-loops in neural stem/progenitor cells undergoing mild replication stress are present primarily in early-replicating, transcribed regions and in genes with promoter GC skew that are associated with cell lineage-specific processes. Surprisingly, most long, neural genes that form recurrent DSB clusters do not show R-loop formation under conditions of mild replication stress. Our findings are consistent with a role of R-loop-associated processes in promoter-proximal DNA break formation in highly transcribed, early replicating regions but suggest that R-loops do not drive replication stress-induced, recurrent DSB cluster formation in most long, neural genes. |
| first_indexed | 2024-04-13T11:24:49Z |
| format | Article |
| id | doaj.art-e95152eb596743f982dfc46e00a7d276 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T11:24:49Z |
| publishDate | 2022-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e95152eb596743f982dfc46e00a7d2762022-12-22T02:48:44ZengNature PortfolioScientific Reports2045-23222022-08-0112111210.1038/s41598-022-17452-0Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cellsSupawat Thongthip0Annika Carlson1Magdalena P. Crossley2Bjoern Schwer3The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of CaliforniaThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of CaliforniaDepartment of Chemical and Systems Biology, Stanford University School of MedicineThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of CaliforniaAbstract Recent studies revealed classes of recurrent DNA double-strand breaks (DSBs) in neural stem/progenitor cells, including transcription-associated, promoter-proximal breaks and recurrent DSB clusters in late-replicating, long neural genes that may give rise to somatic brain mosaicism. The mechanistic factors promoting these different classes of DSBs in neural stem/progenitor cells are not understood. Here, we elucidated the genome-wide landscape of RNA:DNA hybrid structures called “R-loops” in primary neural stem/progenitor cells undergoing aphidicolin-induced, mild replication stress to assess the potential contribution of R-loops to the different, recurrent classes of DNA break “hotspots”. We find that R-loops in neural stem/progenitor cells undergoing mild replication stress are present primarily in early-replicating, transcribed regions and in genes with promoter GC skew that are associated with cell lineage-specific processes. Surprisingly, most long, neural genes that form recurrent DSB clusters do not show R-loop formation under conditions of mild replication stress. Our findings are consistent with a role of R-loop-associated processes in promoter-proximal DNA break formation in highly transcribed, early replicating regions but suggest that R-loops do not drive replication stress-induced, recurrent DSB cluster formation in most long, neural genes.https://doi.org/10.1038/s41598-022-17452-0 |
| spellingShingle | Supawat Thongthip Annika Carlson Magdalena P. Crossley Bjoern Schwer Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells Scientific Reports |
| title | Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells |
| title_full | Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells |
| title_fullStr | Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells |
| title_full_unstemmed | Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells |
| title_short | Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells |
| title_sort | relationships between genome wide r loop distribution and classes of recurrent dna breaks in neural stem progenitor cells |
| url | https://doi.org/10.1038/s41598-022-17452-0 |
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