Resistance of mammalian cells to S(N)1-type methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) generally arises through increased expression of methylguanine methyltransferase (MGMT), which reverts the cytotoxic O(6)-methylguanine ((Me)G) to guanine, or through inactivation of the mismatch repair (MMR) system, which triggers cell death through aberrant processing of (Me)G/T ...

Program death receptor-1 (PD-1) is upregulated in many tumors and in tumor microenvironment, and PD-1 blockade has led to remarkable immune-based anti-tumor responses in across many tumor types. Pembrolizumab, an anti-programmed death 1 checkpoint inhibitor, resulted in a high rate of immune response in 41 patients with previously treated mismatch repair (MMR)-deficient tumor including colorect...

We hypothesized that excessive sympathoactivation observed during strenuous exercise in subjects with heart failure (HF) may result from tonic activation of the muscle metaboreflex (MMR) via hypoperfusion of active skeletal muscle. We studied MMR responses in dogs during treadmill exercise by graded reduction of terminal aortic blood flow (TAQ) before and after induction of HF by rapid ventricu...

Underperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex (MMR). In normal dogs during mild exercise, MMR activation causes large increases in cardiac output (CO) and mean arterial pressure (MAP); however, in heart failure (HF) although MAP increases, the rise in CO is virtually abolished, which may be due to an impaired ability to increase left v...

Mutants of Escherichia coli K-12 unable to excise pyrimidine dimers from their deoxyribonucleic acid (DNA) because of a uvr mutation show a higher survival when plated on a minimal salts medium after exposure to ultraviolet radiation than when plated on a complex medium such as nutrient agar containing yeast extract. This response has been called minimal medium recovery (MMR). Recovery of uvr m...

Loss of DNA mismatch repair (MMR) has been observed in a variety of human cancers. In addition to predisposing to oncogenesis, loss of MMR activity is of concern with respect to the use of chemotherapeutic agents to treat established tumors. Loss of MMR results in drug resistance directly by impairing the ability of the cell to detect DNA damage and activate apoptosis and indirectly by increasi...

The mismatch repair (MMR) system is critical not only for the repair of DNA replication errors, but also for the regulation of mitotic and meiotic recombination processes. In a manner analogous to its ability to remove replication errors, the MMR system can remove mismatches in heteroduplex recombination intermediates to generate gene conversion events. Alternatively, such mismatches can trigge...

Mammalian and Saccharomyces cerevisiae mismatch repair (MMR) proteins catalyze two MMR reactions in vitro. In one, mispair binding by either the MutS homolog 2 (Msh2)-MutS homolog 6 (Msh6) or the Msh2-MutS homolog 3 (Msh3) stimulates 5' to 3' excision by exonuclease 1 (Exo1) from a single-strand break 5' to the mispair, excising the mispair. In the other, Msh2-Msh6 or Msh2-Msh3 activate the Mut...

wnloaded ects in MLH1, as with other mismatch repair (MMR) proteins, are the primary cause of hereditary lyposis colon cancer (HNPCC). Mutations in MMR genes often disrupt mismatch repair and MMR ing functions. However, some HNPCC-associated mutations have unknown pathogenicity. Here, cover an MLH1 clinical mutation with a leucine (L)-to-histidine (H) amino acid change at position at ablates ML...

Mismatch repair (MMR) proteins repair mispaired DNA bases and have an important role in maintaining the integrity of the genome [1]. Loss of MMR has been correlated with resistance to a variety of DNA-damaging agents, including many anticancer drugs [2]. How loss of MMR leads to resistance is not understood, but is proposed to be due to loss of futile MMR activity and/or replication stalling [3...