Cdc48/VCP promotes chromosome morphogenesis by releasing condensin from self-entrapment in chromatin

The morphological transformation of amorphous
chromatin into distinct chromosomes is a hallmark
of mitosis. To achieve this, chromatin must be compacted
and remodeled by a ring-shaped enzyme
complex known as condensin. However, the mechanistic
basis underpinning condensin’s role in chromosome
remodeling has remained elusive. Here we
show that condensin has a strong tendency to trap
itself in its own reaction product during chromatin
compaction and yet is capable of interacting with
chromatin in a highly dynamic manner in vivo. To
resolve this apparent paradox, we identified specific
chromatin remodelers and AAA-class ATPases that
act in a coordinated manner to release condensin
from chromatin entrapment. The Cdc48 segregase
is the central linchpin of this regulatory mechanism
and promotes ubiquitin-dependent cycling of condensin
on mitotic chromatin as well as effective
chromosome condensation. Collectively, our results
show that condensin inhibition by its own reaction
product is relieved by forceful enzyme extraction
from chromatin.