Bacteria and eukaryotic cells employ an arsenal of repair mechanisms to prevent DNA replication errors from becoming permanent, potentially harmful mutations.
Numerous studies have examined how a highly conserved DNA repair protein called MutS identifies rare base-pair mismatches, but how MutS locates a single mismatch among millions of correctly paired nucleotides in a crowded 3D cellular environment is unclear.
Researchers combined single-molecule superresolution imaging with biochemical and genomic approaches to understand how MutS efficiently identifies DNA mismatches during real time in living bacterial cells.
The authors found that one MutS population rapidly explores the entire nucleoid—the cellular region that contains all or most of the genetic material in bacteria. Meanwhile, a slow-moving MutS population moves to the replisome, a large protein complex that carries out DNA replication, even before a mismatch occurs.
The findings suggest that MutS is poised to constantly monitor newly synthesized DNA and quickly detect mistakes that could have deleterious effects on cell growth and survival.
According to the authors, the study demonstrates the potential of the high-resolution imaging approach to reveal how defects in DNA repair processes contribute to cancer and other diseases.