Mitotic chromatin marking governs the segregation of DNA damage
Abstract The faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long-lasting DNA lesions that are segregated...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56090-8 |
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| author | Juliette Ferrand Juliette Dabin Odile Chevallier Matteo Kane-Charvin Ariana Kupai Joel Hrit Scott B. Rothbart Sophie E. Polo |
| author_facet | Juliette Ferrand Juliette Dabin Odile Chevallier Matteo Kane-Charvin Ariana Kupai Joel Hrit Scott B. Rothbart Sophie E. Polo |
| author_sort | Juliette Ferrand |
| collection | DOAJ |
| description | Abstract The faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long-lasting DNA lesions that are segregated during mitosis. How this segregation is controlled is unknown. Here, we uncover a mitotic chromatin-marking pathway that governs the segregation of UV-induced damage in human cells. Our mechanistic analyses reveal two layers of control: histone ADP-ribosylation, and the incorporation of newly synthesized histones at UV damage sites, that both prevent local mitotic phosphorylations on histone H3 serine residues. Functionally, this chromatin-marking pathway controls the segregation of UV damage in the cell progeny with consequences on daughter cell fate. We propose that this mechanism may help preserve the integrity of stem cell compartments during asymmetric cell divisions. |
| format | Article |
| id | doaj-art-f68ac810454d4b73afbfa6341019c9ab |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-f68ac810454d4b73afbfa6341019c9ab2025-01-19T12:30:07ZengNature PortfolioNature Communications2041-17232025-01-0116111210.1038/s41467-025-56090-8Mitotic chromatin marking governs the segregation of DNA damageJuliette Ferrand0Juliette Dabin1Odile Chevallier2Matteo Kane-Charvin3Ariana Kupai4Joel Hrit5Scott B. Rothbart6Sophie E. Polo7Laboratory of Epigenome Integrity, Epigenetics & Cell Fate Centre, UMR7216 CNRS, Université Paris CitéLaboratory of Epigenome Integrity, Epigenetics & Cell Fate Centre, UMR7216 CNRS, Université Paris CitéLaboratory of Epigenome Integrity, Epigenetics & Cell Fate Centre, UMR7216 CNRS, Université Paris CitéLaboratory of Epigenome Integrity, Epigenetics & Cell Fate Centre, UMR7216 CNRS, Université Paris CitéDepartment of Epigenetics, Van Andel InstituteDepartment of Epigenetics, Van Andel InstituteDepartment of Epigenetics, Van Andel InstituteLaboratory of Epigenome Integrity, Epigenetics & Cell Fate Centre, UMR7216 CNRS, Université Paris CitéAbstract The faithful segregation of intact genetic material and the perpetuation of chromatin states through mitotic cell divisions are pivotal for maintaining cell function and identity across cell generations. However, most exogenous mutagens generate long-lasting DNA lesions that are segregated during mitosis. How this segregation is controlled is unknown. Here, we uncover a mitotic chromatin-marking pathway that governs the segregation of UV-induced damage in human cells. Our mechanistic analyses reveal two layers of control: histone ADP-ribosylation, and the incorporation of newly synthesized histones at UV damage sites, that both prevent local mitotic phosphorylations on histone H3 serine residues. Functionally, this chromatin-marking pathway controls the segregation of UV damage in the cell progeny with consequences on daughter cell fate. We propose that this mechanism may help preserve the integrity of stem cell compartments during asymmetric cell divisions.https://doi.org/10.1038/s41467-025-56090-8 |
| spellingShingle | Juliette Ferrand Juliette Dabin Odile Chevallier Matteo Kane-Charvin Ariana Kupai Joel Hrit Scott B. Rothbart Sophie E. Polo Mitotic chromatin marking governs the segregation of DNA damage Nature Communications |
| title | Mitotic chromatin marking governs the segregation of DNA damage |
| title_full | Mitotic chromatin marking governs the segregation of DNA damage |
| title_fullStr | Mitotic chromatin marking governs the segregation of DNA damage |
| title_full_unstemmed | Mitotic chromatin marking governs the segregation of DNA damage |
| title_short | Mitotic chromatin marking governs the segregation of DNA damage |
| title_sort | mitotic chromatin marking governs the segregation of dna damage |
| url | https://doi.org/10.1038/s41467-025-56090-8 |
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