Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks
Summary: DNA double-strand breaks (DSBs) are highly detrimental to cells, as improper repair can result in inheritable genetic rearrangements or cell death. The role of RNA:DNA hybrids (RDHs) in DSB repair remains poorly understood, but their transient accumulation and subsequent resolution are cruc...
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| Language: | English |
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Elsevier
2025-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225014968 |
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| author | Aditya Mojumdar Courtney Granger Martine Lunke Ellis Evans Jennifer A. Cobb |
| author_facet | Aditya Mojumdar Courtney Granger Martine Lunke Ellis Evans Jennifer A. Cobb |
| author_sort | Aditya Mojumdar |
| collection | DOAJ |
| description | Summary: DNA double-strand breaks (DSBs) are highly detrimental to cells, as improper repair can result in inheritable genetic rearrangements or cell death. The role of RNA:DNA hybrids (RDHs) in DSB repair remains poorly understood, but their transient accumulation and subsequent resolution are crucial for accurate repair. The absence of the end-joining factor Nej1 at DSBs significantly reduced RDH levels, which was linked to increased activity of the Dna2 nuclease. Dna2 limits the accumulation of hybrids at DSBs, with levels rising in nuclease-dead Dna2 and deletion of RNH201. Dna2 has a heightened preference for resolving RDHs with 5′ RNA overhangs compared to duplex substrates with 5′ DNA overhangs. This selective resolution by Dna2 helps limit hybrid accumulation at DSBs and promotes DNA resection, a function not shared by Exo1. This study underscores the multifunctional roles of canonical repair factors in ensuring efficient homology-directed repair. |
| format | Article |
| id | doaj-art-e689a5476ec1425484417e696199e2f1 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-e689a5476ec1425484417e696199e2f12025-08-20T04:01:03ZengElsevieriScience2589-00422025-09-0128911323510.1016/j.isci.2025.113235Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaksAditya Mojumdar0Courtney Granger1Martine Lunke2Ellis Evans3Jennifer A. Cobb4Department of Microbiology & Biochemistry, University of Victoria, Victoria, BC V8W 2Y2, CanadaDepartment of Microbiology & Biochemistry, University of Victoria, Victoria, BC V8W 2Y2, CanadaDepartment of Microbiology & Biochemistry, University of Victoria, Victoria, BC V8W 2Y2, CanadaDepartment of Microbiology & Biochemistry, University of Victoria, Victoria, BC V8W 2Y2, CanadaDepartment of Microbiology & Biochemistry, University of Victoria, Victoria, BC V8W 2Y2, Canada; Corresponding authorSummary: DNA double-strand breaks (DSBs) are highly detrimental to cells, as improper repair can result in inheritable genetic rearrangements or cell death. The role of RNA:DNA hybrids (RDHs) in DSB repair remains poorly understood, but their transient accumulation and subsequent resolution are crucial for accurate repair. The absence of the end-joining factor Nej1 at DSBs significantly reduced RDH levels, which was linked to increased activity of the Dna2 nuclease. Dna2 limits the accumulation of hybrids at DSBs, with levels rising in nuclease-dead Dna2 and deletion of RNH201. Dna2 has a heightened preference for resolving RDHs with 5′ RNA overhangs compared to duplex substrates with 5′ DNA overhangs. This selective resolution by Dna2 helps limit hybrid accumulation at DSBs and promotes DNA resection, a function not shared by Exo1. This study underscores the multifunctional roles of canonical repair factors in ensuring efficient homology-directed repair.http://www.sciencedirect.com/science/article/pii/S2589004225014968BiochemistryMolecular biology |
| spellingShingle | Aditya Mojumdar Courtney Granger Martine Lunke Ellis Evans Jennifer A. Cobb Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks iScience Biochemistry Molecular biology |
| title | Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks |
| title_full | Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks |
| title_fullStr | Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks |
| title_full_unstemmed | Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks |
| title_short | Dna2 nuclease resolves RNA:DNA hybrids at double-strand breaks |
| title_sort | dna2 nuclease resolves rna dna hybrids at double strand breaks |
| topic | Biochemistry Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225014968 |
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