EMBL Mouse Biology Unit, Monterotondo, Rome, Italy.
EMBO J. 2012 Sep 12;31(18):3678-90. doi: 10.1038/emboj.2012.214. Epub 2012 Jul 31.
The eukaryotic genome is replicated according to a specific spatio-temporal programme. However, little is known about both its molecular control and biological significance. Here, we identify mouse Rif1 as a key player in the regulation of DNA replication timing. We show that Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication. This effect takes place already in the first S-phase after Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication. Together, these data offer a novel insight into the global regulation and biological significance of the replication-timing programme in mammalian cells.
真核基因组是按照特定的时空程序进行复制的。然而，人们对其分子调控和生物学意义知之甚少。在这里，我们鉴定出小鼠 Rif1 是调控 DNA 复制时间的关键因子。我们发现，原代细胞中 Rif1 的缺失会导致复制时间的整体顺序发生前所未有的改变。这种影响发生在 Rif1 缺失后的第一个 S 期，既不伴有转录景观的改变，也不伴有组成型异染色质的生化特性发生重大变化。此外， Rif1 缺失还会导致 G1/S 期转换和 DNA 复制后的染色质重排缺陷。总之，这些数据为哺乳动物细胞中复制时间程序的全局调控和生物学意义提供了新的见解。
