10 MAliRICE J. liESSMAN 



(leoxy-l^TP in their system and that a specific UTPase is present which 

 converts deoxy-UTP to deoxy-UMP and pyrophosi)hate. They suggest 

 the following scheme for synthesis of deoxythymidylate in E. coli: 



TiMP 



T 



UMP deoxyUMP 



11 T 



UDP -> deoxy UDP 



11 11 -PP 



UTP deoxy UTP 



Another reaction which can jirovide deoxy-UMP rlirectly for deoxy- 

 TMP synthesis is the deamination of deoxycytidylic acid. Scarano 



(1958) has described a specific deoxycytidylate deaminase in sea urchin 

 eggs and rabbit (Scarano and Tolarico, 1959) and Maley and Malcy 



(1959) have extended this work to rat tissues and ciiick embryo. Keck 

 et al. (1960) and Flaks and Cohen (1959b) reported the induction of a 

 specific deoxycytidylate deaminase in T2-infected E. coli. Thus, in any 

 of these systems the following pathway is possible: 



deaminase 



CDP -> dCDP ^ dCMP -^ dUMP-^TMP 



Friedkin (1959b) has published an interesting account of the unique 

 position of thymidylic acid in nucleotide metabolism. 



Recently, Mandel and Borek (1961) reported that the methyl group 

 of the thymine isolated from the ribonucleic acid of E. coli arises from 

 the methyl group of methionine. This interesting observation would 

 suggest that the small amount of thymine in RNA and the thymine in 

 DNA are synthesized by two discrete pathways. 



C. SYNTHESIS OF 5-HYDROXY.METHYLDEOXYCVTmYLIC ACm (dHMP) 



The discoveiy that cytosine is completely replaced by tlio unique 

 pyrimidine, 5-hydroxymethylcytosine (HMC), in the DNA of the T-even 

 bacteriophages (Wyatt and Cohen. 1953) prompted an investigation of 

 the enzymatic steps leading to the synthesis of this comi)ound. Tracer 

 experiments with whole cells had implicated cytosine as a precursor of 

 the pyrimidine ring and the /?-carbon of serine as a precursor of the 

 hydroxymethyl group (Cohen and Weed, 1954) and eliminated methio- 

 nine as the one-carbon donor (Green and Cohen. 1957). Flaks and Cohen 

 (1957, 1959) first reported the synthesis of hydroxymethyldeoxycytidy- 

 late in cell-free extracts of T6r-'-infected E. coli and showed that 

 analogous to thymidylate synthetase the system required tetrahydrofolic 

 acid and fomialdehyde. Tetrahydrofolic acid appears to act catalytically 



