Bacterial DNA repair genes and their eukaryotic homologues: 2. Role of bacterial mutator gene homologues in human disease. Overview of nucleotide pool sanitization and mismatch repair systems.

Abstract

Since the discovery of the first E. coli mutator gene, mutT, most of the mutations inducing elevated spontaneous mutation rates could be clearly attributed to defects in DNA repair. MutT turned out to be a pyrophosphohydrolase hydrolyzing 8-oxodGTP, thus preventing its incorporation into DNA and suppresing the occurrence of spontaneous AT-->CG transversions. Most of the bacterial mutator genes appeared to be evolutionarily conserved, and scientists were continuously searching for contribution of DNA repair deficiency in human diseases, especially carcinogenesis. Yet a human MutT homologue--hMTH1 protein--was found to be overexpressed rather than inactivated in many human diseases, including cancer. The interest in DNA repair contribution to human diseases exploded with the observation that germline mutations in mismatch repair (MMR) genes predispose to hereditary non-polyposis colorectal cancer (HNPCC). Despite our continuously growing knowledge about DNA repair we still do not fully understand how the mutator phenotype contributes to specific forms of human diseases.

The plant Nudix hydrolase family.

“…The first member of the Nudix family to be characterized was the MutT protein of Escherichia coli, hence the original name of this group of enzymes, the MutT family. The MutT hydrolase preferentially hydrolyzes 8-oxo-(d)GTP, a modified nucleotide that occurs in the cellular nucleotide pool as a result of oxidative stress, with the potential to cause both replicational and transcriptional errors (for review see Arczewska & Kuśmierek, 2007).…”

Rapid Acquisition of Linezolid Resistance in Methicillin-Resistant Staphylococcus aureus: Role of Hypermutation and Homologous Recombination

“…NC_002745) [ 18 ]; SNP lists were assembled using Genome Traveler (In Silico Biology, Inc., Mishima, Japan). We especially noted SNPs in hypermutation-related genes, focusing on previously reported loci [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

REPAIRtoire--a database of DNA repair pathways

“…Other DNA lesions interfere with normal cellular transactions, such as DNA replication or transcription, and are deleterious to the cell ( 1 , 2 ). To counteract DNA damage, organisms have evolved various damage prevention and repair systems ( 3–7 ). These systems ensure the stability of DNA and accurate transmission of genetic information by protecting the genome against a large number of different chemical and structural alterations.…”