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KAP1 facilitates reinstatement of heterochromatin after DNA replication

机译:KAP1促进DNA复制后异染色质的恢复

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摘要

During cell division, maintenance of chromatin features from the parental genome requires their proper establishment on its newly synthetized copy. The loss of epigenetic marks within heterochromatin, typically enriched in repetitive elements, endangers genome stability and permits chromosomal rearrangements via recombination. However, how histone modifications associated with heterochromatin are maintained across mitosis remains poorly understood. KAP1 is known to act as a scaffold for a repressor complex that mediates local heterochromatin formation, and was previously demonstrated to play an important role during DNA repair. Accordingly, we investigated a putative role for this protein in the replication of heterochromatic regions. We first found that KAP1 associates with several DNA replication factors including PCNA, MCM3 and MCM6. We then observed that these interactions are promoted by KAP1 phosphorylation on serine 473 during S phase. Finally, we could demonstrate that KAP1 forms a complex with PCNA and the histone-lysine methyltransferase Suv39h1 to reinstate heterochromatin after DNA replication.
机译:在细胞分裂过程中,要维持亲本基因组的染色质特征,需要在新合成的拷贝上正确建立染色质特征。异染色质中表观遗传标记的丢失(通常富含重复元素)会危害基因组稳定性,并允许通过重组进行染色体重排。然而,如何在有丝分裂中维持与异染色质相关的组蛋白修饰仍然知之甚少。已知KAP1充当介导局部异染色质形成的阻遏物复合物的支架,并且先前已证明其在DNA修复过程中起重要作用。因此,我们调查了该蛋白在异色区复制中的假定作用。我们首先发现KAP1与几种DNA复制因子相关,包括PCNA,MCM3和MCM6。然后,我们观察到在S期,丝氨酸473上的KAP1磷酸化促进了这些相互作用。最后,我们可以证明KAP1与PCNA和组蛋白-赖氨酸甲基转移酶Suv39h1形成复合物,以在DNA复制后恢复异染色质。

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