Pch2(TRIP13): controlling cell division through regulation of HORMA domains

During meiotic and mitotic cell divisions, numerous chromosomal processes are essential for the faithful transmission of the genetic material. Pch2(TRIP13), a generally conserved member of the AAA(+) ATPase (AAA(+)--ATPases associated with diverse cellular activities) family of ATPases, is rapidly emerging as a key regulator of specific chromosomal events. During the meiotic program, it is involved in controlling G2/prophase processes such as DNA break formation and recombination, checkpoint signaling, and chromosome synapsis. Excitingly, recent work has also implicated a role for Pch2(TRIP13) in wiring of the checkpoint that guards the metaphase-to-anaphase transition. For several of these functions, the Hop1, Rev7, and Mad2 (HORMA) domain-containing proteins Hop1(HORMAD), Mad2, and p31(COMET) are important downstream clients or cofactors of Pch2(TRIP13). Here, I will discuss our current understanding of the function of Pch2(TRIP13) during meiotic and mitotic cell divisions, with a focus on its enzymatic role towards HORMA domain-containing clients.