The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins

Yumi Kim; Scott C Rosenberg; Christine L Kugel; Nora Kostow; Ofer Rog; Vitaliy Davydov; Tiffany Y Su; Abby F Dernburg; Kevin D Corbett

doi:10.1016/j.devcel.2014.09.013

The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins

Dev Cell. 2014 Nov 24;31(4):487-502. doi: 10.1016/j.devcel.2014.09.013. Epub 2014 Nov 6.

Authors

Yumi Kim¹, Scott C Rosenberg², Christine L Kugel³, Nora Kostow¹, Ofer Rog¹, Vitaliy Davydov³, Tiffany Y Su³, Abby F Dernburg⁴, Kevin D Corbett⁵

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3220, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA; Life Sciences Division, Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, Berkeley, CA 94720, USA.
² Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0660, USA; Ludwig Institute for Cancer Research, San Diego Branch, San Diego, La Jolla, CA 92093-0660, USA.
³ Ludwig Institute for Cancer Research, San Diego Branch, San Diego, La Jolla, CA 92093-0660, USA.
⁴ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3220, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA; Life Sciences Division, Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences, Berkeley, CA 94720, USA. Electronic address: afdernburg@lbl.gov.
⁵ Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0660, USA; Ludwig Institute for Cancer Research, San Diego Branch, San Diego, La Jolla, CA 92093-0660, USA. Electronic address: kcorbett@ucsd.edu.

Abstract

Proteins of the HORMA domain family play central, but poorly understood, roles in chromosome organization and dynamics during meiosis. In Caenorhabditis elegans, four such proteins (HIM-3, HTP-1, HTP-2, and HTP-3) have distinct but overlapping functions. Through combined biochemical, structural, and in vivo analysis, we find that these proteins form hierarchical complexes through binding of their HORMA domains to cognate peptides within their partners' C-terminal tails, analogous to the "safety belt" binding mechanism of Mad2. These interactions are critical for recruitment of HIM-3, HTP-1, and HTP-2 to chromosome axes. HTP-3, in addition to recruiting the other HORMA domain proteins to the axis, plays an independent role in sister chromatid cohesion and double-strand break formation. Finally, we find that mammalian HORMAD1 binds a motif found both at its own C terminus and at that of HORMAD2, indicating that this mode of intermolecular association is a conserved feature of meiotic chromosome structure in eukaryotes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caenorhabditis elegans / cytology
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / metabolism*
Cell Cycle Proteins / metabolism*
Chromosome Pairing / genetics*
Chromosome Segregation / physiology
Chromosomes / metabolism*
Meiosis / physiology*
Mutation / genetics
Synaptonemal Complex / metabolism*

Substances

Caenorhabditis elegans Proteins
Cell Cycle Proteins

Associated data

PDB/4TRK
PDB/4TZJ
PDB/4TZL
PDB/4TZM
PDB/4TZN
PDB/4TZO
PDB/4TZQ
PDB/4TZS

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding