ABSTRACT

Dihydrofolate reductase (Dhfr) is a ubiquitous enzyme that is essential for the de novo synthesis of purines, thymidylate, and glycine. The existence of cell lines containing multiple copies of the Dhfr gene has made many aspects of the cloning and analysis of the gene much easier. For example, mouse Dhfr cDNA made from amplified cell lines was abundant enough to permit screening cDNA clones by complementation of Escherichia coli, as well as by standard colony screening with enriched cDNA probes. The most surprising aspect of the mouse Dhfr promoter region was the discovery that it was acting bidirectional. A more complete review on the mammalian Dhfr locus has recently been published and should be consulted for further information. All the mammalian Dhfr genes that have been analyzed have been found to have a very complex transcriptional pattern. The mouse, hamster, and human genes all have multiple 5' and 3' ends.