Aging alters DNA structure-induced genetic instability in mice.
Saved in:
| Title: | Aging alters DNA structure-induced genetic instability in mice. |
|---|---|
| Authors: | Li, Tonia T.1, Wang, Guliang1, D'Amico, Alexandra M.1, Christensen, Laura A.1, Vasquez, Karen M.1 karen.vasquez@austin.utexas.edu |
| Source: | Proceedings of the National Academy of Sciences of the United States of America. 4/14/2026, Vol. 123 Issue 15, p1-11. 18p. |
| Subjects: | Aging, DNA structure, DNA repair, Mutagenesis, Genetic variation, Apoptosis, Laboratory mice |
| Abstract: | Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the development of age-related genetic disorders such as cancer and Alzheimer's disease. Previously, we found that Z-DNA is mutagenic in mammals; however, the impact of age on Z-DNA-induced genetic instability has not yet been explored. Here, we investigated the effects of aging on Z-DNA-induced genetic instability using a transgenic mutation reporter mouse model. We found that Z-DNA was more mutagenic than control B-DNA in all tissues tested. Contrary to initial expectations, Z-DNA-induced deletions decreased with age, whereas the point mutation frequencies remained unchanged. Our results suggest that while the cleavage activities on Z-DNA were similar in both age groups, the reduction of Z-DNA-induced deletion mutants in aged mice was due to attenuated DNA end-joining efficiency, which is required for the mutagenic processing of Z-DNA, and increased apoptosis. These results provide mechanistic insight into age-associated genetic instability and the aging-cancer link. [ABSTRACT FROM AUTHOR] |
| Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
|---|---|
| Header | DbId: egs DbLabel: Engineering Source An: 193036282 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Aging alters DNA structure-induced genetic instability in mice. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Li%2C+Tonia+T%2E%22">Li, Tonia T.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Wang%2C+Guliang%22">Wang, Guliang</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22D'Amico%2C+Alexandra+M%2E%22">D'Amico, Alexandra M.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Christensen%2C+Laura+A%2E%22">Christensen, Laura A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Vasquez%2C+Karen+M%2E%22">Vasquez, Karen M.</searchLink><relatesTo>1</relatesTo><i> karen.vasquez@austin.utexas.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink>. 4/14/2026, Vol. 123 Issue 15, p1-11. 18p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Aging%22">Aging</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+structure%22">DNA structure</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+repair%22">DNA repair</searchLink><br /><searchLink fieldCode="DE" term="%22Mutagenesis%22">Mutagenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+variation%22">Genetic variation</searchLink><br /><searchLink fieldCode="DE" term="%22Apoptosis%22">Apoptosis</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the development of age-related genetic disorders such as cancer and Alzheimer's disease. Previously, we found that Z-DNA is mutagenic in mammals; however, the impact of age on Z-DNA-induced genetic instability has not yet been explored. Here, we investigated the effects of aging on Z-DNA-induced genetic instability using a transgenic mutation reporter mouse model. We found that Z-DNA was more mutagenic than control B-DNA in all tissues tested. Contrary to initial expectations, Z-DNA-induced deletions decreased with age, whereas the point mutation frequencies remained unchanged. Our results suggest that while the cleavage activities on Z-DNA were similar in both age groups, the reduction of Z-DNA-induced deletion mutants in aged mice was due to attenuated DNA end-joining efficiency, which is required for the mutagenic processing of Z-DNA, and increased apoptosis. These results provide mechanistic insight into age-associated genetic instability and the aging-cancer link. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=193036282 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1073/pnas.2600482123 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 18 StartPage: 1 Subjects: – SubjectFull: Aging Type: general – SubjectFull: DNA structure Type: general – SubjectFull: DNA repair Type: general – SubjectFull: Mutagenesis Type: general – SubjectFull: Genetic variation Type: general – SubjectFull: Apoptosis Type: general – SubjectFull: Laboratory mice Type: general Titles: – TitleFull: Aging alters DNA structure-induced genetic instability in mice. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Li, Tonia T. – PersonEntity: Name: NameFull: Wang, Guliang – PersonEntity: Name: NameFull: D'Amico, Alexandra M. – PersonEntity: Name: NameFull: Christensen, Laura A. – PersonEntity: Name: NameFull: Vasquez, Karen M. IsPartOfRelationships: – BibEntity: Dates: – D: 14 M: 04 Text: 4/14/2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 00278424 Numbering: – Type: volume Value: 123 – Type: issue Value: 15 Titles: – TitleFull: Proceedings of the National Academy of Sciences of the United States of America Type: main |
| ResultId | 1 |
