| Popis: |
This chapter concentrates on the repair mechanism in Escherichia coli, but the lessons learned in this organism should also apply to analogous systems in other organisms. Although there are several distinct DNA mismatch repair systems, in this chapter the term is used to denote the MutSLH system. DNA polymerase III, the replicative enzyme, catalyzes resynthesis of nucleotides and ligation followed by Dam methylation to complete the process. An alternative to the futile cycling model based on double-strand DNA breaks (DSBs) recombinational repair is described in the chapter to explain how mismatch repair sensitizes E. coli dam mutants (and human cells) to methylating agents and cisplatin. In dam mutants there is constant repair of DSBs, and the recombinational capacity of the cell is probably near its maximum. This conclusion is based on the higher basal level of transcription of certain SOS genes in dam cells, suggesting that one or more of the RecA or RuvA or RuvB proteins is limiting. The hypothesis that dam bacteria are sensitive to these agents because of inability to repair all DSBs is quite plausible. An important common theme is the requirement for replication forks to stall or collapse at lesions. The hyperrecombination phenotype is explained by the increased number of DSBs leading to increased initiation of recombination. Together with the roles for Dam methylation in controlling transcription initiation and its role in regulating initiation of chromosome replication and its synchronization, almost all the phenotypic properties can now be explained. |
