Bayliss Christopher D, Sweetman Wendy A, Moxon E Richard
Molecular Infectious Diseases Group, Department of Paediatrics, Weatherall Institute for Molecular Medicine, University of Oxford, John Radcliffe Hospital Headington, Oxford OX3 9DU, UK.
Nucleic Acids Res. 2005 Jan 14;33(1):400-8. doi: 10.1093/nar/gki180. Print 2005.
A feature of Haemophilus influenzae genomes is the presence of several loci containing tracts of six or more identical tetranucleotide repeat units. These repeat tracts are unstable and mediate high frequency, reversible alterations in the expression of surface antigens. This process, termed phase variation (PV), enables H.influenzae to rapidly adapt to fluctuations in the host environment. Perturbation of lagging strand DNA synthesis is known to destabilize simple sequence repeats in yeast and Escherichia coli. By using a chromosomally located reporter construct, we demonstrated that the mutation of an H.influenzae rnhA (encoding RnaseHI) homologue increases the mutation rates of tetranucleotide repeats approximately 3-fold. Additionally, deletion of the Klenow domain of DNA polymerase I (PolI) resulted in a approximately 35-fold increase in tetranucleotide repeat-mediated PV rates. Deletion of the PolI 5'>3' exonuclease domain appears to be lethal. The phenotypes of these mutants suggest that delayed or mutagenic Okazaki fragment processing destabilizes H.influenzae tetranucleotide repeat tracts.
流感嗜血杆菌基因组的一个特点是存在几个位点，这些位点包含六个或更多相同四核苷酸重复单元的片段。这些重复片段不稳定，并介导表面抗原表达的高频、可逆变化。这个过程称为相变（PV），使流感嗜血杆菌能够迅速适应宿主环境的波动。已知滞后链DNA合成的扰动会使酵母和大肠杆菌中的简单序列重复不稳定。通过使用位于染色体上的报告构建体，我们证明流感嗜血杆菌rnhA（编码RnaseHI）同源物的突变使四核苷酸重复的突变率增加约3倍。此外，DNA聚合酶I（PolI）的Klenow结构域的缺失导致四核苷酸重复介导的PV率增加约35倍。PolI 5'>3'核酸外切酶结构域的缺失似乎是致命的。这些突变体的表型表明，延迟或诱变的冈崎片段加工会使流感嗜血杆菌的四核苷酸重复片段不稳定。
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