Every time a cell divides to produce two new daughter cells., the genome must be replicated and evenly divided between those new cells. During this process, DNA undergoes many changes in form. Scientists have now learned more about how cells fold DNA molecules into chromosomes during mitosis so that genetic information is accuratey passed on from one cell to another during division. This basic biological function, which has been outlined in a new report in Science, could help researchers reveal more about stability and repair in DNA molecules; mutations that can cause various diseases including cancer; and the processes of inheritance.
Although scientists have learned a lot about the arrangement of the genome during mitosis, and the complex and dynamic structure of DNA molecules, less is known about how the genome is folded to form chromosomes.
"The work by our team outlines how cells follow a few simple rules to build chromosomes and fold DNA into these tiny, intricate structures during the mitotic phase of cell division," noted Job Dekker, Ph.D., a Howard Hughes Medical Investigator, Professor and Chair at UMass Chan Medical School.
The X shape of chromosomes is well known among many people. When the cell divides, identical halves of each chromosomes forms. These identical halves are known as chromatids, and they remain tethered to the original chromosome by a structure called a centromere. Since we have 48 chromosomes, there are 92 sister chromatids in a cell following division.
Within every chromatid, DNA is folded into loops, which can be rapidly created by DNA-binding cellular machines known as cohesins and condensins.
"We found that these machines extrude loops and as they do so, they race along the chromosomes at extremely high speeds of two to three kilobases per second. More importantly, we discovered a simple set of priorities that define how encounters between these fast-moving machines are resolved by the cell," noted co-first study author Johan Gibcus, Ph.D., an assistant professor at UMass Chan Medical School.
One cohesin machine can extrude loops everywhere in the genome during the interphase portion of cell growth, Gibcus explained.
But during mitosis, two cohesins and two condensins work to generate loops along the chromosomes. When a condensin machine runs into cohesin, which is inevitable, condensin will remove cohesin from the DNA, and then move along to extrude more loops.
Another type of cohesin links the sister chromatids together about once every million bases. If condensin runs into this type of cohesin, condensin skips over it instead of removing it, and goes on extruding. As such, sister chromatids stay linked.
If a condensin encounters another condensin during loops extrusion, they will stop and hold so every chromatid gets arranged into a series of loops.
Sources: University of Massachusetts Chan Medical School, Science
