background: ras-associated domain family 1 (rassf1a) and hypermethylated in cancer (hic1) genes are methylated more frequently in breast cancer. genetic factors that alter the dna methylation levels in normal and tumor tissues could therefore influence the susceptibility to this tumor phenotype. objective: we determined the frequency of aberrant methylation of hic1 and rassf1a gene promoters an...

Background: Ras-associated domain family 1 (RASSF1A) and hypermethylated in cancer (HIC1) genes are methylated more frequently in breast cancer. Genetic factors that alter the DNA methylation levels in normal and tumor tissues could therefore influence the susceptibility to this tumor phenotype. Objective: We determined the frequency of aberrant methylation of HIC1 and RASSF1A gene promoters an...

BACKGROUND Ras-associated domain family 1 (RASSF1A) and hypermethylated in cancer (HIC1) genes are methylated more frequently in breast cancer. Genetic factors that alter the DNA methylation levels in normal and tumor tissues could therefore influence the susceptibility to this tumor phenotype. We determined the frequency of aberrant methylation of HIC1 and RASSF1A gene promoters and their ass...

BACKGROUND Methylenetetrahydrofolate dehydrogenase (MTHFD1) catalyzes three sequential reactions that metabolize derivatives of tetrahydrofolate (THF) in folate-dependent one-carbon metabolism. Impaired MTHFD1 flux has been linked to disturbed lipid metabolism and oxidative stress. However, limited information is available on its relation to the development of atherothrombotic cardiovascular di...

An inborn error of metabolism associated with mutations in the human methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene has been identified. The proband presented with SCID, megaloblastic anemia, and neurologic abnormalities, but the causal metabolic impairment is unknown. SCID has been associated with impaired purine nucleotide metabolism, whereas megaloblastic anemia has been associated ...

The structure of a bifunctional 5,10-methylene-tetrahydrofolate dehydrogenase/cyclohydrolase from Escherichia coli has been determined at 2.5 A resolution in the absence of bound substrates and compared to the NADP-bound structure of the homologous enzyme domains from a trifunctional human synthetase enzyme. Superposition of these structures allows the identification of a highly conserved clust...

Aberrant CpG island hypermethylation in gene promoter regions may be an important epigenetic event in human neoplasias, including breast cancer. Dietary and genetic factors that alter DNA methylation levels in normal and tumour tissues could therefore influence both the susceptibility to this disease and tumour phenotype, respectively. In the present study of 227 breast cancers, we investigated...

Novel methylene tetrahydromethanopterin (H4MPT) dehydrogenase enzymes, named MtdC, were purified after expressing in Escherichia coli genes from, respectively, Gemmata sp. strain Wa1-1 and environmental DNA originating from unidentified microbial species. The MtdC enzymes were shown to possess high affinities for methylene-H4MPT and NADP but low affinities for methylene tetrahydrofolate or NAD....

Polymorphisms in folate pathway genes may influence the susceptibility to acute lymphoblastic leukemia (ALL). DNA was isolated from 245 pediatric ALL patients (cases) and from 500 blood bank donors (controls). Polymorphisms in methylene-tetrahydrofolate reductase (MTHFR 677C>T, 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate deh...

Rapidly proliferating tumors attempt to meet the demands for nucleotide biosynthesis by up-regulating folate pathways that provide the building blocks for pyrimidine and purine biosynthesis. Reduced folates are carriers of one carbon units required for the synthesis of purines, thymidylate and methionine, derived from serine, glycine and formate. As folate metabolism plays a key role in cell pr...