State changes of the HORMA protein ASY1 are mediated by an interplay between its closure motif and PCH2.

Abstract:

:HORMA domain-containing proteins (HORMADs) play an essential role in meiosis in many organisms. The meiotic HORMADs, including yeast Hop1, mouse HORMAD1 and HORMAD2, and Arabidopsis ASY1, assemble along chromosomes at early prophase and the closure motif at their C-termini has been hypothesized to be instrumental for this step by promoting HORMAD oligomerization. In late prophase, ASY1 and its homologs are progressively removed from synapsed chromosomes promoting chromosome synapsis and recombination. The conserved AAA+ ATPase PCH2/TRIP13 has been intensively studied for its role in removing HORMADs from synapsed chromosomes. In contrast, not much is known about how HORMADs are loaded onto chromosomes. Here, we reveal that the PCH2-mediated dissociation of the HORMA domain of ASY1 from its closure motif is important for the nuclear targeting and subsequent chromosomal loading of ASY1. This indicates that the promotion of ASY1 to an 'unlocked' state is a prerequisite for its nuclear localization and chromosomal assembly. Likewise, we find that the closure motif is also necessary for the removal of ASY1 by PCH2 later in prophase. Our work results in a unified new model for PCH2 and HORMADs function in meiosis and suggests a mechanism to contribute to unidirectionality in meiosis.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Yang C,Hu B,Portheine SM,Chuenban P,Schnittger A

doi

10.1093/nar/gkaa527

subject

Has Abstract

pub_date

2020-11-18 00:00:00

pages

11521-11535

issue

20

eissn

0305-1048

issn

1362-4962

pii

5859976

journal_volume

48

pub_type

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