The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit of chromatin assembly factor 1 with proliferating cell nuclear antigen
The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit of chromatin assembly factor 1 with proliferating cell nuclear antigen
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DOI：
10.1038/sj.embor.7400750
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发表时间：
2006-08-01
期刊：
影响因子：
7.7
通讯作者：
Almouzni, Genevieve
中科院分区：
文献类型：
--
作者：
Gerard, Annabelle;Koundrioukoff, Stephane;Almouzni, Genevieve
染色质组装与DNA复制的协调是基因组稳定性所必需的，它需要结合组蛋白沉积的激活和复制起始点的激发。我们在这里报道了组蛋白沉积的关键因子染色质组装因子1(CAF1)与复制激酶CDC7-Dbf4的直接相互作用。我们在S时相特异地分离到一个同时含有CAF1最大亚基(P150)和CDC7-Dbf4激酶的复合体，从而证明了体内这种相互作用的存在。然后我们证明了CDC7-Dbf4激酶有效地磷酸化了P150。这一事件导致P150寡聚状态的改变，促进了与增殖细胞核抗原(PCNA)的结合。相反，CAF1的募集在使用去CDC7的提取物的增殖细胞核抗原/DNA负载分析中被减少。我们的数据将P150定义为该激酶的新靶点，这意味着DNA复制和CAF1功能之间的协调。
The coordination of chromatin assembly with DNA replication, which is essential for genomic stability, requires the combined activation of histone deposition with the firing of replication origins. We report here the direct interaction of chromatin assembly factor 1 (CAF1), a key factor involved in histone deposition, with the replication kinase Cdc7-Dbf4. We isolated a complex containing both the largest subunit of CAF1 (p150) and the Cdc7-Dbf4 kinase specifically in S phase and thus prove the existence of this interaction in vivo. We then show that the Cdc7-Dbf4 kinase efficiently phosphorylates p150. This event induces a change in p150 oligomerization state, which promotes binding to proliferating cell nuclear antigen (PCNA). Conversely, CAF1 recruitment is reduced in a PCNA/DNA loading assay using Cdc7-depleted extracts. Our data define p150 as a new target for this kinase with implications for the coordination between DNA replication and CAF1 functions.