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?4D), demonstrating that all members of the GO system function http://www.selleckchem.com/products/bay80-6946.html together to maintain the mutation frequency in the meningococcus. As the GO system is dispensable for the survival of the meningococcus under oxidative stress (Fig.?4C), we reasoned that other DNA repair systems, including MMR and nucleotide excision repair (NER), might contribute to the repair of ROS-mediated DNA damage. The primary function of the MMR is to remove base�Cbase mismatches or small insertions�Cdeletions loops arising during replication (Yamada et?al., 2002; Li, 2008), whereas, NER is thought to be the most widespread repair pathway and deals mainly with UV-mediated damage (Seeberg, 1978; van Houten et?al., 2002). To determine whether NER and/or MMR can serve a function in excising a ROS-generated DNA lesions we constructed a series of mutants deficient in BER enzymes as well as key MMR or NER enzymes. NER typically consists of UvrA, UvrB, UvrC and the UvrD helicase; dimeric UvrA associates with UvrB forming a recognition complex that searches for structural abnormalities in the DNA helix (Thiagalingam and Grossman, 1993; Goosen and Moolenaar, 2008). In the case of the MMR, MutS is responsible for recognizing abnormal base�Cbase complexes on the daughter strand (Yang et?al., 2000). Therefore, we constructed strains lacking UvrA or MutS to examine the roles of NER and MMR, respectively, during the repair of oxidative DNA damage. The mutS single mutant showed no difference in survival compared with MC58, whereas removing MutS from strain lacking mutM resulted in a significant reduction in survival in the presence of H2O2 and paraquat (Fig.?5A), indicating that the MMR provides a back-up system for the recognition and removal of 8-oxo G, which is not recognized by Nth (Table?1); deletion of MutT in a ��mutM:mutS background did not further impair survival in the face of oxidative stress (not shown). In contrast, the uvrA mutant displayed reduced survival under oxidative stress compared with the parental strain (Fig.?5A), although there was no further decrease in the survival when mutM was removed from the uvrA mutant (��mutM:uvrA). To reveal whether NER and /or MMR serve as back-up systems during BER beyond the stage of base recognition and excision, we tested the sensitivity against H2O2 of mutants lacking UvrA or MutS together with NExo, which processes the 3��-PO4 and aldehyde groups producing by MutM and Nth respectively. Of note, both ��nexo:uvrA and ��nexo:mutS were dramatically attenuated for the survival, recovered at 14% of the level of the nexo mutant (P?