Mitotic chromatin marking governs asymmetric segregation of DNA damage.

bioRxiv : the preprint server for biology Pub Date : 2024-09-28 DOI:10.1101/2023.09.04.556166

Juliette Ferrand, Juliette Dabin, Odile Chevallier, Matteo Kane-Charvin, Ariana Kupai, Joel Hrit, Scott B Rothbart, Sophie E Polo

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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 drives the asymmetric 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.

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有丝分裂染色质标记控制DNA损伤的不对称分离。

完整遗传物质的忠实分离和染色质状态通过有丝分裂细胞分裂的持久化对于在细胞世代中维持细胞功能和身份至关重要。然而，大多数外源性诱变剂会产生持久的DNA损伤，这些损伤在有丝分裂过程中被分离。这种隔离是如何控制的还不得而知。在这里，我们揭示了一种有丝分裂染色质标记途径，它控制着人类细胞中紫外线诱导损伤的分离。我们的机制分析揭示了两层控制：组蛋白ADP核糖基化和新合成的组蛋白在紫外线损伤位点的结合，这两层都可以防止组蛋白H3丝氨酸的局部有丝分裂磷酸化。从功能上讲，这种染色质标记途径驱动细胞子代中紫外线损伤的不对称分离，并对子细胞命运产生潜在影响。我们提出，这种机制可能有助于在不对称细胞分裂过程中保持干细胞区室的完整性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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bioRxiv : the preprint server for biology

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