دورية أكاديمية
KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity
| العنوان: | KAT2-mediated acetylation switches the mode of PALB2 chromatin association to safeguard genome integrity |
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| المؤلفون: | Marjorie Fournier, Amélie Rodrigue, Larissa Milano, Jean-Yves Bleuyard, Anthony M Couturier, Jacob Wall, Jessica Ellins, Svenja Hester, Stephen J Smerdon, László Tora, Jean-Yves Masson, Fumiko Esashi |
| المصدر: | eLife, Vol 11 (2022) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | PALB2, acetylation, chromatin, KAT2, DNA repair, genome stability, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | The tumour suppressor PALB2 stimulates RAD51-mediated homologous recombination (HR) repair of DNA damage, whilst its steady-state association with active genes protects these loci from replication stress. Here, we report that the lysine acetyltransferases 2A and 2B (KAT2A/2B, also called GCN5/PCAF), two well-known transcriptional regulators, acetylate a cluster of seven lysine residues (7K-patch) within the PALB2 chromatin association motif (ChAM) and, in this way, regulate context-dependent PALB2 binding to chromatin. In unperturbed cells, the 7K-patch is targeted for KAT2A/2B-mediated acetylation, which in turn enhances the direct association of PALB2 with nucleosomes. Importantly, DNA damage triggers a rapid deacetylation of ChAM and increases the overall mobility of PALB2. Distinct missense mutations of the 7K-patch render the mode of PALB2 chromatin binding, making it either unstably chromatin-bound (7Q) or randomly bound with a reduced capacity for mobilisation (7R). Significantly, both of these mutations confer a deficiency in RAD51 foci formation and increase DNA damage in S phase, leading to the reduction of overall cell survival. Thus, our study reveals that acetylation of the ChAM 7K-patch acts as a molecular switch to enable dynamic PALB2 shuttling for HR repair while protecting active genes during DNA replication. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/57736; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.57736 |
| URL الوصول: | https://doaj.org/article/5d62dc5a4b634c96b8938dd0c1b86dd9 |
| رقم الأكسشن: | edsdoj.5d62dc5a4b634c96b8938dd0c1b86dd9 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.57736 |