Mismatch repair in Gram-positive bacteria

Abstract

DNA mismatch repair (MMR) is responsible for correcting errors formed during DNA replication. DNA polymerase errors include base mismatches and extra helical nucleotides referred to as insertion and deletion loops. In bacteria, MMR increases the fidelity of the chromosomal DNA replication pathway approximately 100-fold. MMR defects in bacteria reduce replication fidelity and have the potential to affect fitness. In mammals, MMR defects are characterized by an increase in mutation rate and by microsatellite instability. In this review, we discuss current advances in understanding how MMR functions in bacteria lacking the MutH and Dam methylase-dependent MMR pathway.

Mechanisms in E. coli and Human Mismatch Repair (Nobel Lecture)

“…It is also found in many bacterial MutL proteins (Fig. 14), and recent work has shown that like human and yeast MutLα, at least some of these bacterial MutL proteins function as endonucleases (78). The notable exceptions are MutL proteins from bacteria like E. coli and related organisms that rely on d(GATC) methylation to direct mismatch repair, where this motif is conspicuously absent.…”

Addressing the Requirements of High‐Sensitivity Single‐Molecule Imaging of Low‐Copy‐Number Proteins in Bacteria

“…[10]−[12] More recently, several groups have used super‐resolution and single‐molecule fluorescence microscopy to examine intracellular dynamics and localization within this organism. [13]−[19] The traditional methods of single‐molecule tracking and super‐resolution imaging in living bacteria [18]−[26] can be extended to B. subtilis , and complementing these well‐developed methods with biochemical, genetic, and genomic investigations has already led to important discoveries about DNA mismatch detection and mismatch repair (MMR) in B. subtilis . Overall, we have been finding that the proteins that engage in complex DNA repair behaviors are much more dynamic than conventional models would suggest; this motivates further single‐molecule investigations of other DNA replication and repair mechanisms.…”

Evolution of replication machines

“…When the clamp is loaded onto newly replicated DNA for replisome function, the clamp provides directional information to mismatch repair proteins that must distinguish the new strand from the old strand in the daughter duplexes. Although E. coli uses DNA methylation to direct mismatch repair to the new strand, most bacteria do not have this methylation system, and they use the clamp to direct mismatch repair to the new strand, as do eukaryotic cells (Kunkel and Erie, 2005; Lenhart et al ., 2015; Modrich, 2006). Another important function of clamps that mark newly replicated DNA is the assembly of nucleosomes.…”