Multiple dispersed spontaneous mutations: a novel pathway of mutation in a malignant human cell line.

Abstract

We analyzed the nature of spontaneous mutations at the autosomal locus coding for adenine phosphoribosyltransferase in the human colorectal carcinoma cell line SW620 to establish whether distinctive mutational pathways exist that might underlie the more complex genome rearrangements arising in tumor cells. Point mutations occur at a low rate in aprt hemizygotes derived from SW620, largely as a result of base substitutions at G.C base pairs to yield transversions and transitions. However, a novel pathway is evident in the form of multiple dispersed mutations in which two errors, separated by as much as 1,800 bp, fall in the same mutant gene. Such mutations could be the result of error-prone DNA synthesis occurring during normal replication or during long-patch excision-repair of spontaneously arising DNA lesions. This process could also contribute to the chromosomal instability evident in these tumor cells.

• Authors: J Harwood, A Tachibana, M Meuth
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 11 Issue 6 Pg. 3163-70 (Jun 1991) ISSN: 0270-7306 [Print] United States
• PMID: 2038324 (Publication Type: Journal Article)

Chemical References

• DNA, Neoplasm
• Adenine Phosphoribosyltransferase

Topics

• Adenine Phosphoribosyltransferase (genetics)
• Adenocarcinoma (enzymology, genetics)
• Amino Acid Sequence
• Base Sequence
• Blotting, Southern
• Cell Line
• Chromosome Deletion
• Chromosomes, Human, Pair 16
• Colonic Neoplasms (enzymology, genetics)
• DNA, Neoplasm (genetics, isolation & purification)
• Frameshift Mutation
• Gene Rearrangement
• Humans
• Molecular Sequence Data
• Mutation
• Restriction Mapping