Condensins

Condensin is a protein complex that reorganizes sister chromatids into shorter, compact structures during early mitosis. It uses ATP energy to promote chromosome condensation and sister chromatid resolution, transforming the tangled, shapeless mass of post-interphase DNA into individualized chromosomes. This reorganization prevents chromosome breaks and improper segregation during cell division.

Condensin consists of five subunits: two SMC (Structural Maintenance of Chromosomes) proteins—SMC2 and SMC4—connected at their ATPase head domains, plus one kleisin subunit and two HEAT-repeat subunits. The SMC proteins alter DNA arrangement in an ATP-dependent fashion, while the three non-SMC auxiliary subunits differ between condensin I and condensin II complexes.

Condensin II removal results in longer, more flexible chromosomes, chromosome entanglement, and bulky chromatin bridging during anaphase. Condensin I removal leads to shorter, wider chromosomes and disrupted anaphase progression. Both depletions demonstrate that condensins are essential for proper mitotic chromosome formation and cytokinesis completion.

The loop extrusion model explains condensin function: a condensin molecule binds to two nearby DNA sites and slides them in opposite directions, creating a growing DNA loop. Condensins may also form multimers that link distant chromatin segments. These mechanisms work together to compact DNA and facilitate the formation of distinct, organized chromosomes.

Sister chromatid resolution occurs when condensed sister chromatids become distinct structures after sister DNAs are unlinked, or decatenated, by partial removal of cohesins. By metaphase, sister chromatids are loosely connected along their arms but remain tightly linked at centromeres. Condensin facilitates this process by forming ringed structures that encircle DNA loops.

Following DNA replication, sister chromatids are very long and tangled. Attempting to separate them in this state could cause chromosome breaks, improper segregation, and cell death. Condensin gradually reorganizes chromatids into shorter, compact structures during early mitosis, enabling safe and accurate separation during anaphase.

Condensin mutations have been associated with several cancer types. For example, mice with a missense mutation in a condensin II subunit gene developed T cell lymphomas. These findings highlight that condensins are integral to the cell cycle and cell survival, and their dysfunction can lead to malignant transformation.