Physics Colloquium: How protein motors shape chromosomes

Dr. Ed Banigan, Massachusetts Institute of Technology (MIT)

Abstract: Chromosomes are extremely long polymers that are confined to the cell nucleus and spatially organized to facilitate cellular functions, such as gene transcription and genetic inheritance. During each cell cycle, chromosomes are dramatically compacted as cells divide, and they are subsequently reorganized into less compact, spatiotemporally patterned structures after cell division. This nonequilibrium dynamic organization is largely driven by SMC complexes, which are chromosome-bound protein motors that perform a unique activity known as “loop extrusion.” In this process, an SMC complex binds to a chromosome, reels in the chromosome polymer fiber, and extrudes it as a loop. Through theory, simulations, and bioinformatic analyses, I show how the collective activity of these loop-extruding motors organizes chromosomes throughout the cell cycle. First, I show that loop-extruding motors can fold chromosomes during cell division, provided that they satisfy stringent physical requirements. Second, I describe how interactions between loop-extruding motors and other chromosome-bound proteins can dynamically structure the genome. Furthermore, loop extrusion interacts with other genomic processes, such as transcription, which suggests a two-way connection between genome structure and function. Our work illustrates how seemingly subtle microscopic effects can emerge in the spatiotemporal structure of nonequilibrium polymers. In this way, 1D processes, such as active, linear polymer folding, can generate intricate 3D chromosome structures and dynamics, which are critical to genomic function.