Histidine catabolism is a major determinant of methotrexate sensitivity.

ABSTRACT: The chemotherapeutic drug methotrexate inhibits the enzyme dihydrofolate reductase¹, which generates tetrahydrofolate, an essential cofactor in nucleotide synthesis². Depletion of tetrahydrofolate causes cell death by suppressing DNA and RNA production³. Although methotrexate is widely used as an anticancer agent and is the subject of over a thousand ongoing clinical trials⁴, its high toxicity often leads to the premature termination of its use, which reduces its potential efficacy⁵. To identify genes that modulate the response of cancer cells to methotrexate, we performed a CRISPR-Cas9-based screen^6,7. This screen yielded FTCD, which encodes an enzyme-formimidoyltransferase cyclodeaminase-that is required for the catabolism

SUBMITTER: Kanarek N 

PROVIDER: S-EPMC6082631 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature