Lsd1 and lsd2 control programmed replication fork pauses and imprinting in fission yeast

Allyson M. Holmes (1) , Laura Roseaulin (2) , Catherine Schurra (1) , Hervé Waxin (1) , Sarah Lambert (3, 4) , Mikel Zaratiegui (5) , Robert Martienssen (6) , Benoît Arcangioli (1)

1 Dynamique du Génome - Dynamics of the genome
2 DNPG - Dynamique nucléaire et plasticité du génome
3 Institut Curie [Paris]
4 UP11 - Université Paris-Sud - Paris 11
5 RU - Rutgers, The State University of New Jersey [New Brunswick]
6 CSHL - Cold Spring Harbor Laboratory

In the fission yeast Schizosaccharomyces pombe, a chromosomal imprinting event controls the asym-metric 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 repli-cation fork terminators, within the rDNA repeats. These findings reveal a role for the Lsd1/2 demethy-lases in controlling polar replication fork progression, imprint formation, and subsequent asymmetric cell divisions.

Domaines: Biochimie, Biologie Moléculaire

Allyson M. Holmes, Laura Roseaulin, Catherine Schurra, Hervé Waxin, Sarah Lambert, et al.. Lsd1 and lsd2 control programmed replication fork pauses and imprinting in fission yeast. Cell Reports, 2012, 2 (6), pp.1513-1520. ⟨10.1016/j.celrep.2012.10.011⟩. ⟨pasteur-02013826⟩