Replication Origin Selection Regulates the Distribution of Meiotic Recombination

Pei-Yun Jenny Wu,Paul Nurse

doi:10.1016/j.molcel.2014.01.022

Pei-Yun Jenny Wu, Paul Nurse

Open Access

https://doi.org/10.1016/j.molcel.2014.01.022

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Abstract

SummaryThe program of DNA replication, defined by the temporal and spatial pattern of origin activation, is altered during development and in cancers. However, whether changes in origin usage play a role in regulating specific biological processes remains unknown. We investigated the consequences of modifying origin selection on meiosis in fission yeast. Genome-wide changes in the replication program of premeiotic S phase do not affect meiotic progression, indicating that meiosis neither activates nor requires a particular origin pattern. In contrast, local changes in origin efficiencies between different replication programs lead to changes in Rad51 recombination factor binding and recombination frequencies in these domains. We observed similar results for Rad51 when changes in efficiencies were generated by directly targeting expression of the Cdc45 replication factor. We conclude that origin selection is a key determinant for organizing meiotic recombination, providing evidence that genome-wide modifications in replication program can modulate cellular physiology.

Highlights

Eukaryotic DNA synthesis initiates at origins of replication distributed throughout the genome
We investigated the consequences of modifying origin selection on meiosis in fission yeast
We conclude that origin selection is a key determinant for organizing meiotic recombination, providing evidence that genome-wide modifications in replication program can modulate cellular physiology

Summary

Introduction

Eukaryotic DNA synthesis initiates at origins of replication distributed throughout the genome. The program of DNA replication is defined by the timing of firing of each origin during S phase and the probability of usage of each origin in a population of cells, or origin efficiency. Origin selection is modulated by diverse inputs, including cell-cycle regulation, chromatin modifications, nucleotide levels, and gene transcription (Aladjem, 2007; Mechali, 2010; Gilbert, 2007; Cayrou et al, 2010). A genome-wide analysis in fission yeast has suggested that there are significant alterations in origin efficiencies between the mitotic and meiotic cell cycles (Heichinger et al, 2006). We have investigated the impact of origin selection during premeiotic S phase on the subsequent events in meiotic DNA metabolism, characterized by two rounds of chromosome segregation, including a reductional division and interhomolog recombination (Roeder, 1997)

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