Abstract

Meiotic recombination is initiated by the induction of programmed DNA double strand breaks (DSBs). DSB repair promotes homologous interactions and pairing and leads to the formation of crossovers (COs), which are required for the proper reductional segregation at the first meiotic division. In mammals, several hundred DSBs are generated at the beginning of meiotic prophase by the catalytic activity of SPO11. Currently it is not well understood how the frequency and timing of DSB formation and their localization are regulated. Several approaches in humans and mice have provided an extensive description of the localization of initiation events based on CO mapping, leading to the identification and characterization of preferred sites (hotspots) of initiation. This review presents the current knowledge about the proteins known to be involved in this process, the sites where initiation takes place, and the factors that control hotspot localization.

Highlights

  • Meiosis is an essential process whereby the number of chromosomes of diploid germ cells is halved during sexual reproduction

  • One major open challenge concerning the initiation of meiotic recombination is to understand the biochemical mechanisms involved in double strand breaks (DSBs) formation and the function of the proteins that act in concert with SPO11 to promote DSB formation

  • SPO11-dependent meiotic DSBs play an essential role in meiosis by initiating the process that leads to CO formation and ensuring the proper segregation of chromosomes at meiosis I

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Summary

Introduction

Meiosis is an essential process whereby the number of chromosomes of diploid germ cells is halved during sexual reproduction. Genes 2010, 1 chromosomes (homologs) requires specialized mechanisms to connect them, thereby, ensuring their correct orientation at metaphase I and their subsequent migration to opposite spindle poles. Meiotic recombination establishes these physical connections by forming crossovers (COs), which are reciprocal exchanges of genetic material between homologs [1]. One major open challenge concerning the initiation of meiotic recombination is to understand the biochemical mechanisms involved in DSB formation and the function of the proteins that act in concert with SPO11 to promote DSB formation. We will focus on the recent discoveries that have provided new insights into our understanding of meiotic recombination initiation in mammals and we will discuss the possible mechanisms of how initiation sites are chosen in the genome

Initiation of Meiotic Recombination by DSB in Mammals
SPO11: A Universal Catalytic Inducer of Meiotic DSBs
MEI4 and REC114
MEI1: A Protein of Unknown Function
Sites Where Initiation Occurs
The Anatomy of a Hotspot
General Hotspot Properties
Sequence Motifs at Hotspots
Chromatin Structure at Hotspots
The Role of Prdm9 in Hotspot Specification
What Fraction of Hotspots Depends on Prdm9?
From PRDM9 Binding to DSB Formation
Evolutionary Conservation of the Mechanism of Hotspot Specification
Evolution of Initiation Sites in Mammals
Findings
Conclusions
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