title: Pch2 is a hexameric ring ATPase that remodels the chromosome axis protein Hop1.
abstract: In budding yeast the pachytene checkpoint 2 (Pch2) protein regulates meiotic chromosome axis structure by maintaining the domain-like organization of the synaptonemal complex proteins homolog pairing 1 (Hop1) and molecular zipper 1 (Zip1). Pch2 has also been shown to modulate meiotic double-strand break repair outcomes to favor recombination between homologs, play an important role in the progression of meiotic recombination, and maintain ribosomal DNA stability. Pch2 homologs are present in fruit flies, worms, and mammals, however the molecular mechanism of Pch2 function is unknown. In this study we provide a unique and detailed biochemical analysis of Pch2. We find that purified Pch2 is an AAA+ (ATPases associated with diverse cellular activities) protein that oligomerizes into single hexameric rings in the presence of nucleotides. In addition, we show Pch2 binds to Hop1, a critical axial component of the synaptonemal complex that establishes interhomolog repair bias, in a nucleotide-dependent fashion. Importantly, we demonstrate that Pch2 displaces Hop1 from large DNA substrates and that both ATP binding and hydrolysis by Pch2 are required for Pch2-Hop1 transactions. Based on these and previous cell biological observations, we suggest that Pch2 impacts meiotic chromosome function by directly regulating Hop1 localization.
authors.affiliation: Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Ahmad
authors.initials: A
authors.lastname: Jomaa
authors.forename: Joaquin
authors.initials: J
authors.lastname: Ortega
authors.forename: Eric E
authors.initials: EE
authors.lastname: Alani
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000465:Algorithms; D000595:Amino Acid Sequence; D002875:Chromosomes / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005816:Genetic Complementation Test; D005982:Glutathione Transferase / Q000378:metabolism; D006868:Hydrolysis; D008540:Meiosis; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C086672:HOP1 protein, S cerevisiae; D009687:Nuclear Proteins; C528119:Pch2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D005982:Glutathione Transferase; D000251:Adenosine Triphosphatases
keywords: AAA proteins; hexameric ATPase; meiosis