Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Department of Medicine, Department of Biochemistry, University of Washington, Seattle Washington, United States of America.
PLoS Genet. 2021 Sep 2;17(9):e1009714. doi: 10.1371/journal.pgen.1009714. eCollection 2021 Sep.
The spatio-temporal program of genome replication across eukaryotes is thought to be driven both by the uneven loading of pre-replication complexes (pre-RCs) across the genome at the onset of S-phase, and by differences in the timing of activation of these complexes during S phase. To determine the degree to which distribution of pre-RC loading alone could account for chromosomal replication patterns, we mapped the binding sites of the Mcm2-7 helicase complex (MCM) in budding yeast, fission yeast, mouse and humans. We observed similar individual MCM double-hexamer (DH) footprints across the species, but notable differences in their distribution: Footprints in budding yeast were more sharply focused compared to the other three organisms, consistent with the relative sequence specificity of replication origins in S. cerevisiae. Nonetheless, with some clear exceptions, most notably the inactive X-chromosome, much of the fluctuation in replication timing along the chromosomes in all four organisms reflected uneven chromosomal distribution of pre-replication complexes.
真核生物基因组复制的时空程序被认为既受到 S 期起始时预复制复合物（pre-RC）在基因组上不均匀加载的驱动，也受到这些复合物在 S 期激活时间的差异的驱动。为了确定 pre-RC 加载分布本身在多大程度上可以解释染色体复制模式，我们在 budding yeast、fission yeast、mouse 和 human 中绘制了 Mcm2-7 解旋酶复合物（MCM）的结合位点图。我们观察到在这些物种中存在相似的单个 MCM 双六聚体（DH）足迹，但它们的分布存在显著差异：与其他三个生物体相比，budding yeast 中的足迹更加集中，这与 S. cerevisiae 中复制起点的相对序列特异性一致。尽管如此，仍有一些明显的例外，最明显的是失活的 X 染色体，在所有四个生物体的染色体上复制时间的波动在很大程度上反映了 pre-RC 在染色体上的不均匀分布。
