Directionality of DNA replication fork movement strongly affects the generation of spontaneous mutations in Escherichia coli. Export

@article{citeulike:2209369, abstract = {Using a pair of plasmids carrying the rpsL target sequence in different orientations to the replication origin, we analyzed a large number of forward mutations generated in wild-type and mismatch-repair deficient (MMR(-)) Escherichia coli cells to assess the effects of directionality of replication-fork movement on spontaneous mutagenesis and the generation of replication error. All classes of the mutations found in wild-type cells but not MMR(-) cells were strongly affected by the directionality of replication fork movement. It also appeared that the directionality of replication-fork movement governs the directionality of sequence substitution mutagenesis, which occurred in wild-type cells at a frequency comparable to base substitutions and single-base frameshift mutations. A very strong orientation-dependent hot-spot site for single-base frameshift mutations was discovered and demonstrated to be caused by the same process involved in sequence substitution mutagenesis. It is surprising that dnaE173, a potent mutator mutation specific for sequence substitution as well as single-base frameshift, did not enhance the frequency of the hot-spot frameshift mutation. Furthermore, the frequency of the hot-spot frameshift mutation was unchanged in the MMR(-) strain, whereas the mutHLS-dependent mismatch repair system efficiently suppressed the generation of single-base frameshift mutations. These results suggested that the hot-spot frameshift mutagenesis might be initiated at a particular location containing a DNA lesion, and thereby produce a premutagenic replication intermediate resistant to MMR. Significant numbers of spontaneous single-base frameshift mutations are probably caused by similar mechanisms.}, address = {Department of Molecular Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, 630-0101, Japan.}, author = {Yoshiyama, K. and Higuchi, K. and Matsumura, H. and Maki, H.}, citeulike-article-id = {2209369}, citeulike-linkout-0 = {http://dx.doi.org/10.1006/jmbi.2001.4557}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/11292335}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=11292335}, citeulike-linkout-3 = {http://dx.doi.org/http://dx.doi.org/10.1006/jmbi.2001.4557}, citeulike-linkout-4 = {http://dx.doi.org/10.1006/jmbi.2001.4557}, day = {13}, doi = {10.1006/jmbi.2001.4557}, issn = {0022-2836}, journal = {J Mol Biol}, keywords = {palindromes}, month = {April}, number = {5}, pages = {1195--1206}, posted-at = {2008-01-09 02:07:43}, priority = {2}, title = {Directionality of DNA replication fork movement strongly affects the generation of spontaneous mutations in Escherichia coli.}, url = {http://dx.doi.org/10.1006/jmbi.2001.4557}, volume = {307}, year = {2001} }

TY - JOUR ID - citeulike:2209369 L3 - citeulike-article-id:2209369 N2 - Using a pair of plasmids carrying the rpsL target sequence in different orientations to the replication origin, we analyzed a large number of forward mutations generated in wild-type and mismatch-repair deficient (MMR(-)) Escherichia coli cells to assess the effects of directionality of replication-fork movement on spontaneous mutagenesis and the generation of replication error. All classes of the mutations found in wild-type cells but not MMR(-) cells were strongly affected by the directionality of replication fork movement. It also appeared that the directionality of replication-fork movement governs the directionality of sequence substitution mutagenesis, which occurred in wild-type cells at a frequency comparable to base substitutions and single-base frameshift mutations. A very strong orientation-dependent hot-spot site for single-base frameshift mutations was discovered and demonstrated to be caused by the same process involved in sequence substitution mutagenesis. It is surprising that dnaE173, a potent mutator mutation specific for sequence substitution as well as single-base frameshift, did not enhance the frequency of the hot-spot frameshift mutation. Furthermore, the frequency of the hot-spot frameshift mutation was unchanged in the MMR(-) strain, whereas the mutHLS-dependent mismatch repair system efficiently suppressed the generation of single-base frameshift mutations. These results suggested that the hot-spot frameshift mutagenesis might be initiated at a particular location containing a DNA lesion, and thereby produce a premutagenic replication intermediate resistant to MMR. Significant numbers of spontaneous single-base frameshift mutations are probably caused by similar mechanisms. IS - 5 JF - J Mol Biol SN - 0022-2836 AD - Department of Molecular Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, 630-0101, Japan. EP - 1206 TI - Directionality of DNA replication fork movement strongly affects the generation of spontaneous mutations in Escherichia coli. VL - 307 SP - 1195 KW - palindromes AU - Yoshiyama, K AU - Higuchi, K AU - Matsumura, H AU - Maki, H PY - 2001/April/13/ UR - http://dx.doi.org/10.1006/jmbi.2001.4557 ER -