Role for DNA polymerase alpha in epigenetic control of transcriptional silencing in fission yeast

In the fission yeast Schizosaccharomyces pombe, transcriptional silencing a t the mating-type region, centromeres and telomeres is epigenetically contr olled, and results from the assembly of higher order chromatin structures. Chromatin proteins associated with these silenced loci are believed to serv e as molecular bookmarks that help promote inheritance of the silenced stat e during cell division. Specifically, a chromo-domain protein Swi6 is belie ved to be an important determinant of the epigenetic imprint. Here, we show that a mutation in DNA polymerase alpha (pol alpha) affects Swi6 localizat ion at the mating-type region and causes a 45-fold increase in spontaneous transition from the silenced epigenetic state to the expressed state. We al so demonstrate that pol alpha mutant cells are defective in Swi6 localizati on at centromeres and telomeres, Genetic analysis suggests that Pola and Sw i6 are part of the same silencing pathway, Interestingly, we found that Swi 6 directly binds to Pol alpha in vitro. Moreover, silencing-defective mutan t Pol alpha displays reduced binding to Swi6 protein. This work indicates i nvolvement of a DNA replication protein, Pol alpha, in heterochromatin asse mbly and inheritance of epigenetic chromatin structures.