Genetic instability of microsatellite repeat sequences [microsatellite instability (MI)] is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is a result of inactivating mutations in any of several genes involved in a particular pathway of DNA mismatch repair. Sporadic (i.e., nonhereditary) manifestations of several tumor types, including colorec...

AID deaminates C to U in either strand of Ig genes, exclusively producing C:G/G:C to T:A/A:T transition mutations if U is left unrepaired. Error-prone processing by UNG2 or mismatch repair diversifies mutation, predominantly at C:G or A:T base pairs, respectively. Here, we show that transversions at C:G base pairs occur by two distinct processing pathways that are dictated by sequence context. ...

Alterations of DNA mismatch repair genes, primarily demonstrated in hereditary nonpolyposis colorectal carcinomas, were reported to be of relevance for the progression of several sporadic tumours. In this study, the expression and mutations of MLH1, MSH2, PMS1 and PMS2 in a panel of thyroid tumours, including nodular hyperplasia, follicular adenomas and carcinomas, were investigated. The expres...

Patients with Muir-Torre syndrome, an autosomal-dominant familial tumor condition caused by germline mutation of the DNA mismatch repair genes, MSH2 or MLH1, present with tumors of the sebaceous gland and visceral malignancies characterized by microsatellite instability. Here we show development of glioblastoma multiforme in a patient with Muir-Torre syndrome. Immunohistochemical analysis of th...

Oligodeoxynucleotide (ODN)-mediated gene alteration was postulated to occur in two steps, DNA strand pairing and DNA repair. Once alignment has occurred through homologous strand pairing, a single mismatch is formed between an oligonucleotide and one of the target strands. Because of this mismatch, it has been suggested that proteins involved in a mismatch repair pathway (MMR) participate in th...

DNA adenine methylation by DNA adenine methyltransferase (Dam) in Escherichia coli plays an important role in processes such as DNA replication initiation, gene expression regulation, and mismatch repair. In addition, E. coli strains deficient in Dam are hypersensitive to DNA-damaging agents. We used genome microarrays to compare the transcriptional profiles of E. coli strains deficient in Dam ...

Mutations in DNA repair genes lead to increased genomic instability and mutation frequency. These mutations represent potential biomarkers for cancer immunotherapy efficacy, as high tumor mutational burden has been associated with increased neo-antigens and tumor infiltrating lymphocytes. While mismatch repair mutations have successfully predicted response to anti-PD-1 therapy in colorectal and...

Hereditary nonpolyposis colorectal cancer is caused by inherited mutations of mismatch repair genes. We developed monoclonal antibodies to the prototype human mismatch repair gene hMSH2 and used them to detect an immunoreactive protein of M(r) 100,000 in mismatch-proficient cell lines. In addition, a M(r) 150,000 protein coimmunoprecipitated with the hMSH2 gene product in cell lines expressing ...

Yeast Msh2p forms complexes with Msh3p and Msh6p to repair DNA mispairs that arise during DNA replication. In addition to their role in mismatch repair (MMR), the MSH2 and MSH3 gene products are required to remove 3' nonhomologous DNA tails during genetic recombination. The mismatch repair genes MSH6, MLH1, and PMS1, whose products interact with Msh2p, are not required in this process. We have ...

Ig somatic hypermutation contributes to the generation of high-affinity Abs that are essential for efficient humoral defense. The presence of multiple point mutations in rearranged Ig V genes and their immediate flanking sequences suggests that the DNA repair system may not be working properly in correcting point mutations introduced to the restricted region of Ig genes. We examined the DNA rep...