Three genes that participate in the repair of DNA alkylation damage were recently cloned from Saccharomyces cerevisiae: the MGT1 O6-methylguanine DNA methyltransferase gene, the MAG 3-methyladenine DNA glycosylase gene, and the APN1 apurinic/apyrimidinic (AP) endonuclease gene. Altering the expression levels of these three genes produced significant changes in the S. cerevisiae spontaneous muta...

Oligonucleosomes were isolated from [14C]thymidine-labeled HeLa cells by digestion of the nuclei with micrococcal nuclease and were then alkylated with [3H]methylnitrosourea. Nucleosome core particles were also prepared by further digestion of the Oligonucleosomes. The distribution of 3H-labeled methyl groups in the linker versus the core DMA was established by a determi nation of 3H:14Cratios ...

Alkylating agents have long played a central role in the adjuvant therapy of glioblastoma (GBM). More recently, inclusion of temozolomide (TMZ), an orally administered methylating agent with low systemic toxicity, during and after radiotherapy has markedly improved survival. Extensive in vitro and in vivo evidence has shown that TMZ-induced O(6)-methylguanine (O(6)-meG) mediates GBM cell killin...

Ulcerative colitis (UC), a chronic inflammatory condition associated with a predisposition to colon cancer, is frequently characterized by DNA damage in the form of microsatellite instability (MSI). A new report links inflammation in UC with increases in the DNA repair enzymes 3-methyladenine DNA glycosylase and apurinic/apyrimidinic endonuclease, and, paradoxically, with increased MSI. These f...

The presence of 6-methyladenine and 5-methylcytosine at Dam (GATC) and Dcm (CCA/TGG) sites in DNA of mycobacterial species was investigated using isoschizomer restriction enzymes. In all species examined, Dam and Dcm recognition sequences were not methylated indicating the absence of these methyltransferases. On the other hand, high performance liquid chromatographic analysis of genomic DNA fro...

Strains of Neisseria gonorrhoeae were tested for the presence of methyladenine in the DNA sequence GATC by using the site-specific restriction endonucleases MboI and DpnI. It was found that 43 of 83 strains tested contained methylated DNA. When methylation was compared with the auxotype of the organism, 35 of 35 strains with the AHU (arginine-, hypoxanthine-, and uracil-requiring) auxotype and ...

3-Methyladenine (3-MA) inhibits class III phosphoinositide 3-kinase (PI3K) and is widely used as an inhibitor of autophagy. 3-MA has also been shown to stimulate cell death of tumor cells under nutrient-starved conditions by inhibiting autophagy. To explore the possibility of this type of autophagy inhibitors as anticancer drugs, we examined the effects of 3-MA on the phenotypes of highly metas...