Homeologous recombination and mismatch repair during transformation in Streptococcus pneumoniae: saturation of the Hex mismatch repair system.

Abstract

The ability of the Hex generalized mismatch repair system to prevent recombination between partially divergent (also called homeologous) sequences during transformation in Streptococcus pneumoniae was investigated. By using as donor in transformation cloned fragments 1.7-17.5% divergent in DNA sequence from the recipient, it was observed that the Hex system prevents chromosomal integration of the least and the most divergent fragments but frequently fails to do so for other fragments. In the latter case, the Hex system becomes saturated (inhibited) due to an excess of mismatches: it is unable to repair a single mismatch located elsewhere on the chromosome. Further investigation with chromosomal donor DNA, carrying only one genetically marked divergent region, revealed that a single divergent fragment can lead to saturation of the Hex system. Increase in cellular concentration of either HexA, the MutS homologue that binds mismatches, or HexB, the MutL homologue for which the essential role in repair as yet remains obscure, was shown to restore repair ability in previously saturating conditions. Investigation gf heterospecific transformation by chromosomal DNA from two related streptococcal species, Streptococcus oralis and Streptococcus mitis, also revealed complete saturation of the Hex system. Therefore the Hex system is not a barrier to interspecies recombination in S. pneumoniae. These results are discussed in light of those described for the Mut system of Escherichia coli.

Mismatch Repair Regulates Homologous Recombination, but Has Little Influence on Antigenic Variation, in Trypanosoma brucei

“…In Bacillus subtilis, in contrast, MMR appears to play only a small role (63), with the recombination machinery largely responsible for substrate selection (although this might be a consequence of transformation occurring under starvation conditions (33)). Streptococcus pneumoniae seems to fall somewhere between these extremes (64,65). In S. cerevisiae, MMR is the sole determinant of decreased recombination up to around 10% sequence divergence, and thereafter the recombination machinery itself becomes sensitive to base mismatches (48).…”

Altered Replication and Inverted Repeats Induce Mismatch Repair-Independent Recombination between Highly Diverged DNAs in Yeast

“…Since bacterial Tn5 LIRs are frequently deleted during conjugation (7), suggesting that they form stem-like structures in the single-stranded DNA during transfer, they might help to overcome the barrier to recombination in bacterial interspecies crosses (44). Along with this, the role of MMR should be investigated, since the impact of MMR on homeologous recombination appears to depend on the route of recombination in bacteria (1,2,32,44) as well as yeast (5,21,42,43).…”

Sensing of DNA non‐homology lowers the initiation of meiotic recomination in yeast

“…in somatic pairing), this mechanism might be extremely useful in cells containing a genome with repeated DNA sequences, because it would prevent potential ectopic DNA/DNA interactions leading to chromosomal translocations when gene conversion events are associated with reciprocal exchanges. In this perspective, this meiotic process, which monitors the initiation of recombination and behaves as an anti-initiation mechanism, would precede the anti-recombinogenic properties of the mismatch repair mutS/L system found in bacteria (Rayssiguier et al 1989;Humbert et al 1995) and in yeast (Hunter et al 1996). Altogether, these processes would be implicated in the maintenance of chromosomal stability, in the monitoring of sequence divergence, and in the establishment of the genetic barrier between species (Wagner & Radman 1993).…”