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KAP1 facilitates reinstatement of heterochromatin after DNA replication

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干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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During cell division, not only is the genome duplicated, but the maintenance of chromatin features on the parental DNA and their propagation onto daughter strands is a challenge. The loss of epigenetic marks on heterochromatin, typically enriched in repetitive elements, could lead to genome instability and chromosomal rearrangements via recombination. How they are maintained across cell division and most importantly which critical molecular players are involved is poorly understood. KAP1 is known to act as a scaffold for a repressor complex that mediates local heterochromatin formation, and plays an important role during DNA repair. Here we identify in KAP1 a novel role for the replication of heterochromatic regions. First, we observed that KAP1 associates with several DNA replication factors including PCNA, MCM3 and MCM6. Second, we found that these interactions are modulated by KAP1 phosphorylation during S phase. Finally we could demonstrate that KAP1 recruits HP1 and the histone-lysine methyltransferases Suv39h1 and Suv420h1. Based on these data, we propose a model for KAP1 involvement in maintaining heterochromatin during DNA replication and thereby preventing genome instability.
提供机构:
EPFL
创建时间:
2022-02-20
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