1000 VOLUME 24 NUMBER 11 NOVEMBER 2017 NAture StructurAL & moLecuLAr bIoLogY Emerging evidence indicates that somatic mutations in cancer genomes are nonrandomly distributed and are influenced by factors such as genomic context and DNA secondary structures, chromatin organization, transcriptional activity, and replication timing1–11. Local variation in the mutation burden stems from variability...

The mycobacterium-specific gene Rv2719c was found to be expressed primarily from a promoter that was clearly DNA damage inducible independently of RecA. Upstream of the transcriptional start site for this promoter, sequence motifs resembling those observed previously at the RecA-independent, DNA damage-inducible recA promoter were identified, and the -10 motif was demonstrated by mutational ana...

BACKGROUND Mutation analysis of proto-oncogene c-kit (c-kit) is advisable before starting treatment with tyrosine kinase inhibitors in dogs with mast cell tumor (MCT), including those with metastatic disease. Testing is usually performed on primary tumors, assuming that c-kit mutation status does not change in metastasis. HYPOTHESIS/OBJECTIVES To give an insight into the mutational processes ...

We studied the mutagenicity of the proximate bladder carcinogen, N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) in embryonic fibroblasts of the Big Blue mouse. Treatment of these cells with increasing concentrations of N-OH-AABP for 24 h resulted in a dose-dependent increase in mutation frequency of the cII transgene up to 12.8-fold over the background. Single base substitutions comprised 86% of t...

Uracil-initiated base excision DNA repair was conducted using homozygous mouse embryonic fibroblast DNA polymerase beta (+/+) and (-/-) cells to determine the error frequency and mutational specificity associated with the completed repair process. Form I DNA substrates were constructed with site-specific uracil residues at U.A, U.G, and U.T targets contained within the lacZalpha gene of M13mp2 ...

AIM To report the early vitreous involvement in a rare familial amyloidotic polyneuropathy (FAP) mutation and associated vitreous vascular endothelial growth factor (VEGF) levels. DESIGN Observational case series. METHODS Review of clinical, pathological, photographic, and angiographic records of two FAP siblings with severe vitreous involvement. Laboratory ELISA analysis of vitreous sample...

AIM To develop a diagnostic DNA chip to detect mutations in the betaigh3 gene causing the most common corneal dystrophies (CDs). METHODS Samples from 98 people, including patients with betaigh3-associated CDs (beta-aCDs), were examined. Specific primer and probe sets were designed to examine exons 4 and 12 of the betaigh3 gene, in order to identify mutant and wild-type alleles. Mutations were...

Down syndrome (DS) children have a unique genetic susceptibility to develop leukemia, in particular, acute megakaryocytic leukemia (AMkL) associated with somatic GATA1 mutations. The study of this genetic susceptibility with the use of DS as a model of leukemogenesis has broad applicability to the understanding of leukemia in children overall. On the basis of the role of GATA1 mutations in DS A...

Cancer therapy largely depends on chemotherapeutic agents that generate DNA lesions. However, our understanding of the nature of the resulting lesions as well as the mutational profiles of these chemotherapeutic agents is limited. Among these lesions, DNA interstrand crosslinks are among the more toxic types of DNA damage. Here, we have characterized the mutational spectrum of the commonly used...