RNA insertion in DNA as the imprint moiety: the fission yeast paradigm

This review elaborates on the findings of a new report which possibly resolves the biochemical nature of a novel type of DNA imprint as ribonucleotide and the mechanism of its formation during cell differentiation in fission yeast. The process of mating-type switching in fission yeast, Schizosaccharomyces pombe, displays characteristics of a typical mammalian stem cell lineage, wherein a cell divides to produce an identical cell and a differentiated cell after every two cell divisions. This developmental asymmetry has been ascribed to play a role in generation of a DNA strand-specific imprint at the mat1 locus during lagging strand synthesis and its segregation to one of the two daughter cells by the process of asymmetric, semi-conservative DNA replication. The nature of this imprint and mechanisms of its generation have been a subject of research and debate. A recent report by Singh et al. (Nucleic Acids Res 47:3422-3433. https://doi.org/10.1093/nar/gkz092 , 2019) provides compelling evidence in support of a ribonucleotide as the imprint moiety within the mat1 DNA and demonstrates the role of Mcm10/Cdc23, an important, evolutionarily conserved component of DNA replication machinery in eukaryotes, in installing the imprint through a non-canonical primase activity and interaction with DNA Polα and Swi1. The high degree of conservation of DNA replication machinery, especially the presence of the T7 gene 4 helicase/primase domain in the mammalian orthologs of Mcm10 suggests that similar mechanisms of DNA imprinting may play a role during cell differentiation in metazoans.