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

Area of Science:

• Cell Biology
• Genetics
• Molecular Biology

Background:

• Chromosomal imprinting in Schizosaccharomyces pombe regulates mating-type switching.
• DNA replication orientation at the mating-type locus is critical for imprinting.
• The precise factors and mechanisms underlying imprinting remain largely unknown.

Purpose of the Study:

• To identify the factors involved in replication fork pause at the mat1 locus (MPS1).
• To elucidate the role of lysine-specific demethylase (Lsd1) in imprinting and asymmetric cell division.
• To understand the mechanism by which Lsd1/2 controls replication fork progression and termination.

Main Methods:

• Investigated the dependence of replication fork pause (MPS1) on Lsd1 in fission yeast.
• Assessed the requirement of Lsd1 or Lsd2 amine oxidase activity for imprinting.
• Analyzed the role of the Lsd1/2 complex in controlling replication fork terminators within rDNA repeats.

Main Results:

• Replication fork pause at the mat1 locus (MPS1) is dependent on lysine-specific demethylase Lsd1.
• Lsd1 or Lsd2 amine oxidase activity is necessary for imprinting, acting upstream of Swi1 and Swi3.
• The Lsd1/2 complex regulates replication fork terminators in rDNA repeats.

Conclusions:

• Lysine-specific demethylases Lsd1/2 play a crucial role in controlling polar replication fork progression.
• Lsd1/2 activity is essential for imprint formation, which dictates asymmetric cell divisions.
• These findings reveal a novel function for Lsd1/2 in regulating DNA replication dynamics and cell fate determination.