Limits of Chromosome Compaction by Loop-Extruding Motors

• Main Authors: Banigan, Edward J (Author), Mirny, Leonid A (Author)
• Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor), Massachusetts Institute of Technology. Department of Physics (Contributor)
• Format: Article
• Language: English
• Published: American Physical Society (APS), 2020-07-23T16:11:02Z.
• Subjects: Article
• Online Access: Get fulltext

 During mitosis, human chromosomes are linearly compacted about 1000-fold by loop-extruding motors. Recent experiments have shown that condensins extrude DNA loops but in a "one-sided" manner. This contrasts with existing models, which predict that symmetric, "two-sided" loop extrusion accounts for mitotic chromosome compaction. We explore whether one-sided extrusion, as it is currently seen in experiments, can compact chromosomes by developing a mean-field theoretical model for polymer compaction by motors that actively extrude loops and dynamically turnover. The model establishes a stringent upper bound of only about tenfold for compaction by strictly one-sided extrusion. We confirm this result with stochastic simulations. Thus, strictly one-sided extrusion as it has been observed so far cannot be the sole mechanism of chromosome compaction. However, as shown by the model, other two-sided or effectively two-sided mechanisms can achieve sufficient compaction.