Molecular mechanism targeting condensin for chromosome condensation

Abstract

Genomes are organised into DNA loops by the Structural Maintenance of Chromosomes (SMC) proteins. SMCs establish functional chromosomal sub-domains for DNA repair, gene expression and chromosome segregation, but how SMC activity is specifically targeted is unclear. Here, we define the molecular mechanism targeting the condensin SMC complex to specific chromosomal regions in budding yeast. A conserved pocket on the condensin HAWK subunit Ycg1 binds to chromosomal receptors carrying a related motif, CR1. In early mitosis, CR1 motifs in receptors Sgo1 and Lrs4 recruit condensin to pericentromeres and rDNA, to facilitate sister kinetochore biorientation and rDNA condensation, respectively. We additionally find that chromosome arm condensation begins as sister kinetochores come under tension, in a manner dependent on the Ycg1 pocket. We propose that multiple CR1-containing proteins recruit condensin to chromosomes and identify several additional candidates based on their sequence. Overall, we uncover the molecular mechanism that targets condensin to functionalise chromosomal domains to achieve accurate chromosome segregation during mitosis.

Synopsis

How the condensin complex is recruited to genomic domains to promote their condensation is incompletely understood. This study identifies a generalised molecular mechanism by which condensin is targeted to specific chromosomal loci.

• Budding yeast condensin is recruited to chromosomes via a conserved binding pocket on its Ycg1/CAP-G subunit.

• The Ycg1 pocket binds CR1 motifs in several chromosomal proteins.

• CR1 motifs in Sgo1 and Lrs4 recruit condensin to pericentromeres and rDNA, respectively.

• Condensin recruited to pericentromeres by Sgo1 promotes sister kinetochore biorientation in the absence of spindle tension.

• Chromosome arm and rDNA condensation is initiated by spindle tension, dependent on the Ycg1 binding pocket.

Abstract

A pocket in the CAP-G/Ycg1 subunit binds CR1 motifs in several chromosomal proteins to recruit condensin to specific chromosomal regions.