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The multiple activities of enterobacterial RecBCD helicase-nuclease are coordinated by Chi recombination hotspots (5\u2032 GCTGGTGG 3\u2032) recognized during DNA unwinding. Chi is recognized in a tunnel in RecC but activates the RecB nuclease,\u2009&gt;\u200925 \u01fa away. How the Chi-dependent signal travels this long distance has been unknown. We found a Chi hotspot-deficient mutant in the RecB helicase domain located\u2009&gt;\u200945 \u01fa from both the Chi-recognition site and the nuclease active site. This unexpected observation led us to find additional mutations that reduced or eliminated Chi hotspot activity in each subunit and widely scattered throughout RecBCD. Each mutation alters the intimate contact between one or another pair of subunits in crystal or cryoEM structures of RecBCD bound to DNA. Collectively, these mutations span a path\u2009about\u2009185 \u01fa long from the Chi recognition site to the nuclease active site. We discuss these surprising results in the context of an intramolecular signal transduction accounting for many previous observations.<\/jats:p>","DOI":"10.1038\/s41598-020-73078-0","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T06:04:33Z","timestamp":1604556273000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Chi hotspot control of RecBCD helicase-nuclease by long-range intramolecular signaling"],"prefix":"10.1038","volume":"10","author":[{"given":"Susan K.","family":"Amundsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew F.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"key":"73078_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1128\/MMBR.05026-11","volume":"76","author":"GR Smith","year":"2012","unstructured":"Smith, G. 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