Linked spontaneous CG----TA mutations at CpG sites in the gene for protein kinase regulatory subunit.
CG----TA transitions at CpG sequences account for many human point mutations and are thought to result from hydrolytic deamination of 5-methylcytosine residues in these sites. The gene for regulatory subunit of murine cyclic AMP-dependent protein kinase has two closely linked CpG sites, one of which is a strong hotspot for spontaneous CG----TA mutations leading to cyclic AMP resistance in S49 mouse lymphoma cells. About 5% of mutants with a spontaneous mutation at this CpG site had also acquired a second CG----TA mutation at the nearby CpG site. The two mutations were always at first positions of the Arg codons in which they occurred, and they were always together in a single regulatory subunit allele. Their linked appearance could be attributed to neither the selection conditions nor the preexistence of one mutation in the target cells. The high frequency of these double mutants suggests that their lesions result not from hydrolytic deamination but rather from an endogenous enzymatic mechanism.
Steinberg
R A
RA
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Gorman
K B
KB
D000818:Animals; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D000242:Cyclic AMP / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001120:Arginine; D003062:Codon; D000242:Cyclic AMP; D015226:Dinucleoside Phosphates; D011494:Protein Kinases; C015772:CpG dinucleotide