Getting there: understanding the chromosomal recruitment of the AAA+ ATPase Pch2/TRIP13 during meiosis

Abstract

The generally conserved AAA+ ATPase Pch2/TRIP13 is involved in diverse aspects of meiosis, such as prophase checkpoint function, DNA break regulation, and meiotic recombination. The controlled recruitment of Pch2 to meiotic chromosomes allows it to use its ATPase activity to influence HORMA protein-dependent signaling. Because of the connection between Pch2 chromosomal recruitment and its functional roles in meiosis, it is important to reveal the molecular details that govern Pch2 localization. Here, we review the current understanding of the different factors that control the recruitment of Pch2 to meiotic chromosomes, with a focus on research performed in budding yeast. During meiosis in this organism, Pch2 is enriched within the nucleolus, where it likely associates with the specialized chromatin of the ribosomal (r)DNA. Pch2 is also found on non-rDNA euchromatin, where its recruitment is contingent on Zip1, a component of the synaptonemal complex (SC) that assembles between homologous chromosomes. We discuss recent findings connecting the recruitment of Pch2 with its association with the Origin Recognition Complex (ORC) and reliance on RNA Polymerase II-dependent transcription. In total, we provide a comprehensive overview of the pathways that control the chromosomal association of an important meiotic regulator.

Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation

“…Regardless, our observations provide mechanistic insights into the specific recruitment of Mer2 to meiotic chromosomes. For example, our model might explain how Mer2 can specifically be recruited to meiotic chromosomes, and not form spurious interactions with non-chromosomal Hop1: non-chromosomal, monomeric Hop1 is thought to be largely present in the intramolecular ‘closed’ form (unless it is converted into the ‘open/unbuckled’ state by Pch2/TRIP13, which is thought to promote rapid chromosomal incorporation of Hop1) ( Cardoso da Silva and Vader, 2021 ; Raina and Vader, 2020 ). Conversely, it might explain how DSB activity is negatively regulated by chromosome synapsis.…”

Novel mechanistic insights into the role of Mer2 as the keystone of meiotic DNA break formation

“…We believe that our observations provide mechanistic insights into the specific recruitment of Mer2 to meiotic chromosomes. For example, this model might explain how Mer2 can specifically be recruited to meiotic chromosomes, and not form spurious interactions with nonchromosomal Hop1: non-chromosomal, monomeric Hop1 is thought to be largely present in the intramolecular 'closed' form (unless it is converted into the 'open/unbuckled' state by Pch2/TRIP13, which is thought to promote rapid chromosomal incorporation of Hop1) 30,42 . Conversely, it might explain how DSB activity is negatively regulated by chromosome synapsis.…”