Journal article icon

Journal article

Destabilization of tetranucleotide repeats in Haemophilus influenzae mutants lacking RnaseHI or the Klenow domain of PolI

Abstract:
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 ∼3-fold. Additionally, deletion of the Klenow domain of DNA polymerase I (PolI) resulted in a ∼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.
Publication status:
Published
Peer review status:
Peer reviewed

Actions


Access Document


Files:
Publisher copy:
10.1093/nar/gki180

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
Weatherall Insti. of Molecular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
Weatherall Insti. of Molecular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
Weatherall Insti. of Molecular Medicine
Role:
Author


Publisher:
Oxford University Press
Journal:
Nucleic Acids Research More from this journal
Volume:
33
Issue:
1
Pages:
400–408
Publication date:
2005-01-01
Edition:
Publisher's version
DOI:
EISSN:
1362-4962
ISSN:
0305-1048


Language:
English
Subjects:
UUID:
uuid:de7490aa-9324-451e-b724-5196c34e5869
Local pid:
ora:8065
Deposit date:
2014-02-24

Terms of use



Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP