DNA-measuring Wadjet SMC ATPases restrict smaller circular plasmids by DNA cleavage

Mol Cell. 2022 Dec 15;82(24):4727-4740.e6. doi: 10.1016/j.molcel.2022.11.015.

Abstract

Structural maintenance of chromosome (SMC) complexes fold DNA by loop extrusion to support chromosome segregation and genome maintenance. Wadjet systems (JetABCD/MksBEFG/EptABCD) are derivative SMC complexes with roles in bacterial immunity against selfish DNA. Here, we show that JetABCD restricts circular plasmids with an upper size limit of about 100 kb, whereas a linear plasmid evades restriction. Purified JetABCD complexes cleave circular DNA molecules, regardless of the DNA helical topology; cleavage is DNA sequence nonspecific and depends on the SMC ATPase. A cryo-EM structure reveals a distinct JetABC dimer-of-dimers geometry, with the two SMC dimers facing in opposite direction-rather than the same as observed with MukBEF. We hypothesize that JetABCD is a DNA-shape-specific endonuclease and propose the "total extrusion model" for DNA cleavage exclusively when extrusion of an entire plasmid has been completed by a JetABCD complex. Total extrusion cannot be achieved on the larger chromosome, explaining how self-DNA may evade processing.

Keywords: DNA loop extrusion; JetABCD; SMC complexes; Wadjet; bacterial defense system; eptABCD; horizontal gene transfer; mksBEFG; mukBEF; plasmid restriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases* / genetics
  • Adenosine Triphosphatases* / metabolism
  • Cell Cycle Proteins / genetics
  • Chromosomes / metabolism
  • Chromosomes, Bacterial / genetics
  • Chromosomes, Bacterial / metabolism
  • DNA / genetics
  • DNA Cleavage*
  • Plasmids / genetics

Substances

  • Adenosine Triphosphatases
  • DNA
  • Cell Cycle Proteins