Checkpoint control in meiotic prophase: Idiosyncratic demands require unique characteristics

Abstract

Chromosomal transactions such as replication, recombination and segregation are monitored by cell cycle checkpoint cascades. These checkpoints ensure the proper execution of processes that are needed for faithful genome inheritance from one cell to the next, and across generations. In meiotic prophase, a specialized checkpoint monitors defining events of meiosis: programmed DNA break formation, followed by dedicated repair through recombination based on interhomolog (IH) crossovers. This checkpoint shares molecular characteristics with canonical DNA damage checkpoints active during somatic cell cycles. However, idiosyncratic requirements of meiotic prophase have introduced unique features in this signaling cascade. In this review, we discuss the unique features of the meiotic prophase checkpoint. While being related to canonical DNA damage checkpoint cascades, the meiotic prophase checkpoint also shows similarities with the spindle assembly checkpoint (SAC) that guards chromosome segregation. We highlight these emerging similarities in the signaling logic of the checkpoints that govern meiotic prophase and chromosome segregation, and how thinking of these similarities can help us better understand meiotic prophase control. We also discuss work showing that, when aberrantly expressed, components of the meiotic prophase checkpoint might alter DNA repair fidelity and chromosome segregation in cancer cells. Considering checkpoint function in light of demands imposed by the special characteristics of meiotic prophase helps us understand checkpoint integration into the meiotic cell cycle machinery.

Keywords: Checkpoint; Chromosome segregation; DNA double strand breaks; HORMA; Meiosis; Mitosis; Recombination; Spatial separation.