DNA Mismatch Correction

Modrich, P

doi:10.1146/annurev.biochem.56.1.435

Cited by 106 publications

(141 citation statements)

References 61 publications

(135 reference statements)

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“…The dam gene defect induces the SOS response by aberrant strand break during mismatch repair (Modrich, 1987). To avoid this influence, we introduced mutS::Tn10 to NA001, which leads to a failure to break DNA strands.…”

Section: Suppression Of Dnaacos By a Dam Null Mutationmentioning

confidence: 99%

Overinitiation of chromosome replication in the Escherichia coli dnaAcos mutant depends on activation of oriC function by the dam gene product

Katayama

Akimitsu

Mizushima

et al. 1997

Molecular Microbiology

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Section: Suppression Of Dnaacos By a Dam Null Mutationmentioning

confidence: 99%

Overinitiation of chromosome replication in the Escherichia coli dnaAcos mutant depends on activation of oriC function by the dam gene product

Katayama

Akimitsu

Mizushima

et al. 1997

Molecular Microbiology

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“…In normal cells, initiating oncogenic mutation is considered essential to promote a "preneoplastic change," which, if unrepaired, is then followed by proliferation and acquisition of cellular survival capacity, allowing accumulation of additional mutations (8)(9)(10). Potentially oncogenic mutations can be antagonized by DNA repair mechanisms, some mediated by members of the mismatch repair (MMR) family, which corrects base mispairings or repairs larger insertion/deletion loops (IDL; refs [11][12][13][14]. In the MMR system, three homologs of the bacterial MutS protein-Msh2, Msh3, and Msh6-form heterodimers that recognize DNA damage (15).…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin-like Protein 2 Accelerates Carcinogenesis by Activating Chronic Inflammation and Oxidative Stress

Aoi

Endo

Kadomatsu

et al. 2014

Molecular Cancer Research

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Chronic inflammation has received much attention as a risk factor for carcinogenesis. We recently reported that Angiopoietin-like protein 2 (Angptl2) facilitates inflammatory carcinogenesis and metastasis in a chemically induced squamous cell carcinoma (SCC) of the skin mouse model. In particular, we demonstrated that Angptl2-induced inflammation enhanced susceptibility of skin tissues to "preneoplastic change" and "malignant conversion" in SCC development; however, mechanisms underlying this activity remain unclear. Using this model, we now report that transgenic mice overexpressing Angptl2 in skin epithelial cells (K14-Angptl2 Tg mice) show enhanced oxidative stress in these tissues. Conversely, in the context of this model, Angptl2 knockout (KO) mice show significantly decreased oxidative stress in skin tissue as well as a lower incidence of SCC compared with wild-type mice. In the chemically induced SCC model, treatment of K14-Angptl2 Tg mice with the antioxidant N-acetyl cysteine (NAC) significantly reduced oxidative stress in skin tissue and the frequency of SCC development. Interestingly, K14-Angptl2 Tg mice in the model also showed significantly decreased expression of mRNA encoding the DNA mismatch repair enzyme Msh2 compared with wild-type mice and increased methylation of the Msh2 promoter in skin tissues. Msh2 expression in skin tissues of Tg mice was significantly increased by NAC treatment, as was Msh2 promoter demethylation. Overall, this study strongly suggests that the inflammatory mediator Angptl2 accelerates chemically induced carcinogenesis through increased oxidative stress and decreased Msh2 expression in skin tissue.

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“…In addition, Dam methylation is very important in the E. coli mismatch repair system formed by MutSL and MutH (reviewed in refs. 12,13). Dam methylation also helps to regulate chromosome replication by maintaining the methylation of the origin of chromosome replication.…”

mentioning

confidence: 99%

Structure of the bacteriophage T4 DNA adenine methyltransferase

Yang

Horton

Zhou

et al. 2003

Nat Struct Mol Biol

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DNA-adenine methylation at certain GATC sites plays a pivotal role in bacterial and phage gene expression as well as bacterial virulence. We report here the crystal structures of the bacteriophage T4Dam DNA adenine methyltransferase (MTase) in a binary complex with the methyl-donor product S-adenosyl-L-homocysteine (AdoHcy) and in a ternary complex with a synthetic 12-bp DNA duplex and AdoHcy. T4Dam contains two domains: a seven-stranded catalytic domain that harbors the binding site for AdoHcy and a DNA binding domain consisting of a five-helix bundle and a β-hairpin that is conserved in the family of GATC-related MTase orthologs. Unexpectedly, the sequence-specific T4Dam bound to DNA in a nonspecific mode that contained two Dam monomers per synthetic duplex, even though the DNA contains a single GATC site. The ternary structure provides a rare snapshot of an enzyme poised for linear diffusion along the DNA.DNA MTases catalyze methyl group transfer from donor S-adenosyl-L-methionine (AdoMet), producing S-adenosyl-L-homocysteine (AdoHcy) and methylated DNA. Although most prokaryote DNA MTases are components of restriction-modification systems, some MTases are not associated with cognate restriction enzymes, such as the Escherichia coli DNA adenine MTase (Dam). This enzyme methylates an exocyclic amino nitrogen (N6) of the adenine in GATC 1,2 . Dam MTase gene orthologs are widespread among enteric bacteria and their bacteriophages (see Fig. 1 legend). Dam methylation is not essential for the viability of E. coli, unless it is combined with certain other mutations 3 ; however, Dam is an essential gene in Vibrio cholerae and Yersinia pesudotuberculosis, at least under the tested growth conditions 4 . Dam methylation is essential for the virulence of Salmonella serovar typhimurium in a murine model of typhoid fever [5][6][7] . These observations COMPETING INTERESTS STATEMENTThe authors declare that they have no competing financial interests. NIH Public Access RESULTS Overall structure of DamThe monomeric Dam structure contains 9 β-strands and 11 α-helices (Fig. 1). The Nterminal region (residues 1-52) and C-terminal region (residues 149-259) come together, forming the catalytic domain (green in Figs. 1 and 2a) with a seven-stranded β-sheet, a characteristic feature of the class-I AdoMet-dependent MTases 28 . The N-terminal helices αZ and αA are located on one side of the β-sheet, and helices αC, αD1 and αD2 and αE are on the other side. Between strands β2 and β3 is a separate domain, which we designate as the target-recognition domain (TRD). TRD is composed of a five-helix bundle (αB1-αB5) (yellow in Figs. 1 and 2a) and a 25-residue segment containing a β-hairpin (β8 and β9) inserted between helices αB4 and αB5 (red). The overall dimensions of the molecule are 55 × 34 × 28 Å, with an open cleft located between the catalytic domain (green) and the TRD (yellow and red). Conserved residues and the effects of mutationsBased on the linear arrangement of conserved motifs in DNA MTases, T4Dam is classified in the...

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DNA Mismatch Correction

Cited by 106 publications

References 61 publications

Overinitiation of chromosome replication in the Escherichia coli dnaAcos mutant depends on activation of oriC function by the dam gene product

Overinitiation of chromosome replication in the Escherichia coli dnaAcos mutant depends on activation of oriC function by the dam gene product

Angiopoietin-like Protein 2 Accelerates Carcinogenesis by Activating Chronic Inflammation and Oxidative Stress

Structure of the bacteriophage T4 DNA adenine methyltransferase

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