Lsd1 and Lsd2 Control Programmed Replication Fork Pauses and Imprinting in Fission Yeast

SummaryIn the fission yeast Schizosaccharomyces pombe, a chromosomal imprinting event controls the asymmetric pattern of mating-type switching. The orientation of DNA replication at the mating-type locus is instrumental in this process. However, the factors leading to imprinting are not fully identified and the mechanism is poorly understood. Here, we show that the replication fork pause at the mat1 locus (MPS1), essential for imprint formation, depends on the lysine-specific demethylase Lsd1. We demonstrate that either Lsd1 or Lsd2 amine oxidase activity is required for these processes, working upstream of the imprinting factors Swi1 and Swi3 (homologs of mammalian Timeless and Tipin, respectively). We also show that the Lsd1/2 complex controls the replication fork terminators, within the rDNA repeats. These findings reveal a role for the Lsd1/2 demethylases in controlling polar replication fork progression, imprint formation, and subsequent asymmetric cell divisions.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The lysine-specific demethylase, Lsd1, is a mating-type switching mutant ► Lsd1 is essential for replication fork pausing at the mat1 locus ► Lsd1 is essential for replication fork arrest at the replication fork block at rDNA loci ► Lsd1 and Lsd2 act in a redundant manner for replication fork pausing