Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720.
Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):E2030-E2039. doi: 10.1073/pnas.1721573115. Epub 2018 Feb 13.
In , heterochromatin structures required for transcriptional silencing of the and loci are duplicated in coordination with passing DNA replication forks. Despite major reorganization of chromatin structure, the heterochromatic, transcriptionally silent states of and are successfully maintained throughout S-phase. Mutations of specific components of the replisome diminish the capacity to maintain silencing of and through replication. Similarly, mutations in histone chaperones involved in replication-coupled nucleosome assembly reduce gene silencing. Bridging these observations, we determined that the proliferating cell nuclear antigen (PCNA) unloading activity of Elg1 was important for coordinating DNA replication forks with the process of replication-coupled nucleosome assembly to maintain silencing of and through S-phase. Collectively, these data identified a mechanism by which chromatin reassembly is coordinated with DNA replication to maintain silencing through S-phase.
在真核生物中,与通过 DNA 复制叉协调的转录沉默的 和 基因座所需的异染色质结构被复制。尽管染色质结构发生了重大重组,但 和 基因的异染色质、转录沉默状态在整个 S 期都能成功维持。复制体特定成分的突变会降低通过复制维持 和 沉默的能力。同样,参与复制偶联核小体组装的组蛋白伴侣的突变会降低基因沉默。将这些观察结果联系起来,我们确定增殖细胞核抗原(PCNA)从 Elg1 上的卸载活性对于协调 DNA 复制叉与复制偶联核小体组装过程以维持 S 期的 和 基因沉默是重要的。总的来说,这些数据确定了一种机制,通过该机制,染色质的重新组装与 DNA 复制相协调,以维持 S 期的沉默。