Polo Sophie E, Roche Danièle, Almouzni Geneviève
Laboratory of Nuclear Dynamics and Genome Plasticity, UMR 218 CNRS/Institut Curie, 26 rue d'Ulm, 75248 Paris cedex 5, France.
Cell. 2006 Nov 3;127(3):481-93. doi: 10.1016/j.cell.2006.08.049.
Chromatin organization is compromised during the repair of DNA damage. It remains unknown how and to what extent epigenetic information is preserved in vivo. A central question is whether chromatin reorganization involves recycling of parental histones or new histone incorporation. Here, we devise an approach to follow new histone deposition upon UV irradiation in human cells. We show that new H3.1 histones get incorporated in vivo at repair sites. Remarkably we find that H3.1, which is deposited during S phase, is also incorporated outside of S phase. Histone deposition is dependent on nucleotide excision repair (NER), indicating that it occurs at a postrepair stage. The histone chaperone chromatin assembly factor 1 (CAF-1) is directly involved in the histone deposition process in vivo. We conclude that chromatin restoration after damage cannot rely simply on histone recycling. New histone incorporation at repair sites both challenges epigenetic stability and possibly contributes to damage memory.
在DNA损伤修复过程中，染色质组织会受到破坏。目前尚不清楚表观遗传信息在体内是如何以及在多大程度上得以保留。一个核心问题是染色质重组是否涉及亲本组蛋白的循环利用或新组蛋白的掺入。在此，我们设计了一种方法来追踪人类细胞在紫外线照射后新组蛋白的沉积情况。我们发现新的H3.1组蛋白在体内修复位点被掺入。值得注意的是，我们发现，在S期沉积的H3.1也会在S期之外被掺入。组蛋白沉积依赖于核苷酸切除修复（NER），这表明它发生在修复后的阶段。组蛋白伴侣染色质组装因子1（CAF-1）在体内直接参与组蛋白沉积过程。我们得出结论，损伤后的染色质修复不能仅仅依赖于组蛋白的循环利用。修复位点上新组蛋白的掺入既挑战了表观遗传稳定性，也可能有助于损伤记忆。
