Many essential processes in biology share a common fundamental step—establishing physical contact between distant segments of DNA. How fast this step is accomplished sets the “speed limit” for the larger-scale processes it enables, whether the process is antibody production by the immune system or tissue differentiation in a developing embryo. This naturally leads us to ask, How long does it take for DNA segments that are strung out over millions of base pairs along the chromatin fiber to find each other in the crowded cell? This question, fundamental to biology, can be recognized as the physics problem of the first-passage time, or the waiting time for the first encounter. Here, we review a number of approaches to revealing the physical principles by which cells solve, with astonishing efficiency, the first-passage problem for remote genomic interactions.


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