Coordination of DNA Replication and Histone Modification by the Rik1-Dos2 Complex

Histone modification marks play an important role in many chromatin processes(1,2). During DNA replication, both heterochromatin and euchromatin are disrupted ahead of the replication fork and then reassembled into their original epigenetic states behind the fork(3,4). How the histone marks are faithfully inherited during each generation is still poorly understood. In fission yeast RNA interference (RNAi)-mediated histone methylation is cell-cycle regulated. Centromere repeats are transiently transcribed at S phase and processed into small interference RNAs (siRNAs) by RITS and RDRC complexes(5-7). The small RNAs, in concert with silencing factors, including Dos1/Clr8, Dos2/Clr7, Rik1 and Lid2, promote heterochromatic H3K9 methylation by a histone methyltransferase, Clr4(8-13). H3K9 methylation serves as a binding site for Swi6, a structural and functional homolog of metazoan Heterochromatin Protein 1 (HP1)(14). Here we characterize a silencing complex, which contains Dos2, Rik1, Mms19, and Cdc20 (DNA polymerase epsilon). The complex regulates RNA Pol II activity in heterochromatin, and is required for DNA replication and heterochromatin assembly. Our findings provide a molecular link between DNA replication and histone methylation, shedding light on how epigenetic marks are transmitted during each cell cycle.