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Orientation of DNA replication establishes mating-type switching pattern in S. pombe
1Gene Regulation and Chromosome Biology Laboratory, ABL-Basic Research Program, NCI Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Nature
|July 17, 1999
Summary
Fission yeast cells undergo mating-type switching through a DNA modification at mat1. Replication timing dictates this imprint, influencing developmental potential in daughter cells.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- Haploid fission yeast, Schizosaccharomyces pombe, possess two mating types (mat1).
- Mating-type switching occurs in one in four granddaughter cells after asymmetric divisions.
- This process involves genetic information transfer from donor loci (mat2-P/mat3-M) to mat1.
Purpose of the Study:
- To elucidate the molecular mechanism of mating-type switching in Schizosaccharomyces pombe.
- To identify the nature of the genetic imprint at mat1.
- To investigate the role of DNA replication in imprinting and switching.
Main Methods:
- Biochemical analysis to identify DNA modifications.
- DNA replication studies using altered replication origins.
- Two-dimensional gel electrophoresis to analyze replication timing.
Main Results:
- The genetic imprint is a strand-specific, alkali-labile DNA modification at mat1.
- The double-stranded DNA break is an artifact of DNA purification, not the primary event.
- mat1 is preferentially replicated by centromere-distal origins, leading to imprinting during lagging-strand synthesis.
- Altering replication origins impacts imprinting and switching efficiencies.
Conclusions:
- DNA replication machinery plays a crucial role in conferring differential developmental potential to sister cells.
- Strand-specific DNA modification during replication dictates mating-type switching.
- The findings reveal a novel link between replication timing and epigenetic regulation.
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