A time and place for DNA replication

The ability to accurately copy genomic DNA at the appropriate time before cells divide is critical to all aspects of growth and development. Yet the molecular events involved are poorly understood for most eukaryotes.

A research team led by Hisao Masai of the Tokyo Metropolitan Institute of Medical Science, Japan, reports that the timing and site of initiation of DNA replication hinges on the protein called Rif1¹: these events are almost random in fission yeast that lack this protein. The researchers revealed the role of Rif1 by screening for mutants that rescue another fission yeast mutant with defective DNA replication.

Biologists previously thought that Rif1 binds only to telomeres, the repetitive sequences at the ends of chromosomes. However, Masai and colleagues showed that it also binds to specific sites on the chromosome arms. Most Rif1 binding sites do not overlap with the initiation sites (‘origins’); however, some occur close to ‘dormant’ origins, where initiation is normally suppressed, but is activated in cells lacking Rif1.

The researchers speculate that Rif1 may specifically alter the architecture of chromatin, the dynamic mixture of DNA and proteins that controls when the genome is duplicated or read.

It remains to be established whether human Rif1 functions in the same manner as Rif1 from fission yeast.