Mcm2-Ctf4-Polα 轴促进亲本组蛋白 H3-H4 向滞后链转移。
The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands.
机构信息
Institute for Cancer Genetics, Department of Pediatrics and Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
出版信息
Mol Cell. 2018 Oct 4;72(1):140-151.e3. doi: 10.1016/j.molcel.2018.09.001. Epub 2018 Sep 20.
Although essential for epigenetic inheritance, the transfer of parental histone (H3-H4) tetramers that contain epigenetic modifications to replicating DNA strands is poorly understood. Here, we show that the Mcm2-Ctf4-Polα axis facilitates the transfer of parental (H3-H4) tetramers to lagging-strand DNA at replication forks. Mutating the conserved histone-binding domain of the Mcm2 subunit of the CMG (Cdc45-MCM-GINS) DNA helicase, which translocates along the leading-strand template, results in a marked enrichment of parental (H3-H4) on leading strand, due to the impairment of the transfer of parental (H3-H4) to lagging strands. Similar effects are observed in Ctf4 and Polα primase mutants that disrupt the connection of the CMG helicase to Polα that resides on lagging-strand template. Our results support a model whereby parental (H3-H4) complexes displaced from nucleosomes by DNA unwinding at replication forks are transferred by the CMG-Ctf4-Polα complex to lagging-strand DNA for nucleosome assembly at the original location.
尽管组蛋白（H3-H4）四聚体的转移对于表观遗传遗传至关重要，但对于复制 DNA 链中含有表观遗传修饰的亲本组蛋白（H3-H4）四聚体的转移知之甚少。在这里，我们表明 Mcm2-Ctf4-Polα 轴有助于将亲本（H3-H4）四聚体转移到复制叉处的滞后链 DNA 上。突变 Cdc45-MCM-GINS（CMG）DNA 解旋酶 Mcm2 亚基的保守组蛋白结合域，该亚基沿前导链模板易位，会导致亲本（H3-H4）在前导链上明显富集，这是由于亲本（H3-H4）向滞后链的转移受损。在 Ctf4 和 Polα 引发酶突变体中也观察到类似的影响，这些突变体破坏了位于滞后链模板上的 Polα 与 CMG 解旋酶的连接。我们的结果支持这样一种模型，即通过 CMG-Ctf4-Polα 复合物将在复制叉处由 DNA 解旋从核小体中置换出的亲本（H3-H4）复合物转移到滞后链 DNA 上，以便在原始位置进行核小体组装。
Zotero 插件