DNA Replication Timing: From Basic Mechanisms to Biological Functions

Dear Colleagues,

DNA replication is a fundamental biological process required for copying genetic and epigenetic material prior to cell division. In prokaryotes, DNA replication occurs at well-defined loci known as replication origins. The situation, however, is more complex in eukaryotes due to the differences in genome size, and genomic contents, such as repeat load. It is estimated that there could be tens of thousands of putative replication origins in the eukaryotic genome that fire stochastically in the S phase. Eukaryotic replication origins are also regulated in a strict temporal manner, with some origins firing early and others firing late. By labeling proliferating cells with thymidine analogs such as BrdU (Bromodeoxyuridine, 5-bromo-2'-deoxyuridine) or EdU (5-Ethynyl-2´-deoxyuridine), it has become possible to map the replication timing of the genome into early, mid or late replicating regions. These studies have revealed that in higher eukaryotes, e.g., mammals, replication domains are intricately linked with large genomic compartments known as TADs (topologically-associating domains) and LADs (lamina-associated domains). More importantly, replication timing appears to play a role in mammalian development, manifested by a difference in replication timing between the active or inactive X-chromosomes in females. Further, defects in replication timing could lead to impairment of genome stability and cancer. Given the multifaceted roles of replication timing in fundamental regulation of the genome, and in development and disease, in this Special Issue, we will focus on the basic molecular mechanisms that determine replication timing and the biological aspects that are linked with replication timing. In particular, we will address the following areas:

1) Molecular and genomic techniques to determine replication timing;

2) Role of genetic and epigenetic cues to modulate replication timing;

3) Role of replication timing in development and differentiation;

4) Genomic defects and diseases associated with replication timing.

Elucidation of the above areas will broaden our understanding of the basic biological processes regulated by replication timing and will also provide us with new ideas for designing therapeutic tools against diseases like cancer by focusing on replication timing.

Dr. Jafar Sharif
Dr. Shin-Ichiro Takebayashi
Guest Editor

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