Methylenetetrahydrofolate reductase (MTHFR) is necessary for the synthesis of methionine and S-adenosylmethionine, which is necessary for CNS (re-)myelination. The MTHFR variant c.1298A>C was associated with the development of relapsing remitting multiple sclerosis (RRMS) in a German population. This study aimed at analyzing whether further genetic variants of methionine metabolism are associat...

To identify proteins that interact with the yeast proliferating cell nuclear antigen (PCNA), we used a genetic approach to isolate mutations that compensate for the defects in cold-sensitive (Cs(-)) mutants of yeast PCNA (POL30). Because the cocrystal structure of human PCNA and a p21(WAF1/CIP1) peptide shows that the interdomain region of PCNA is a site of p21 interaction, we specifically look...

Membrane transporter proteins may influence the sensitivity of cancer cells to anticancer drugs that can be recognized as substrates. The purpose of this study was to identify proteins that play a key role in the drug sensitivity of stomach and breast cancer cell lines by measuring the absolute protein expression levels of multiple transporters and other membrane proteins and examining their co...

BACKGROUND Genome instability is a hallmark of cancer and plays a critical role in generating the myriad of phenotypes selected for during tumor progression. However, the mechanisms that prevent genome rearrangements remain poorly understood. RESULTS To elucidate the mechanisms that ensure genome stability, we screened a collection of candidate genes for suppressors of gross chromosomal rearr...

BACKGROUND Impaired homocysteine metabolism is associated with a number of vasculopathies including extracranial aneurysms. We analyzed the possible association of nine genetic variants of homocysteine metabolism with the occurrence of intracranial aneurysms. METHODS Caucasian patients (n = 255) treated at two German hospitals for intracranial aneurysms and local controls (n = 348) were genot...

Low folate status may be a consequence of suboptimal intake, transport or cellular utilization of folate and, together with elevated homocysteine, is a recognized risk factor or marker for several human pathologies. As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk v...

To identify in vivo pathways that compensate for impaired proliferating cell nuclear antigen (PCNA or Pol30p in yeast) activity, we performed a synthetic lethal screen with the yeast pol30-104 mutation. We identified nine mutations that display synthetic lethality with pol30-104; three mutations affected the structural gene for the large subunit of replication factor C (rfc1), which loads PCNA ...