dictyNews
Electronic Edition
Volume 33, number 6
August 28, 2009
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Abstracts
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Xpf and not the Fanconi anaemia proteins or Rev3 accounts for the
extreme
resistance to cisplatin in Dictyostelium discoideum
Xiao-Yin Zhang, Judith Langenick, David Traynor, M. Madan Babu, Rob R.
Kay
and Ketan J. Patel
Medical Research Council, Laboratory for Molecular Biology, Hills Road,
Cambridge CB2 0QH, UK
PLoS Genetics, in press
Organisms like Dictyostelium discoideum, often referred to as DNA damage
"extremophiles", can survive exposure to extremely high doses of
radiation
and DNA crosslinking agents. These agents form highly toxic DNA
crosslinks
that cause extensive DNA damage. However little is known about how
Dictyostelium and the other “extremophiles” can tolerate and repair such
large numbers of DNA crosslinks. Here we describe a comprehensive
genetic
analysis of crosslink repair in Dictyostelium discoideum. We analyse
three
gene groups that are crucial for a replication coupled repair process
that
removes DNA crosslinks in higher eukarya: The Fanconi anaemia pathway
(FA), translesion synthesis (TLS), and nucleotide excision repair. Gene
disruption studies unexpectedly reveal that the FA genes and the TLS
enzyme Rev3 play minor roles in tolerance to crosslinks in
Dictyostelium.
However, disruption of the Xpf nuclease subcomponent results in striking
hypersensitivity to crosslinks. Genetic interaction studies reveal that
although Xpf functions with FA and TLS gene products, most Xpf mediated
repair is independent of these two gene groups. These results suggest
that Dictyostelium utilises a distinct Xpf nuclease-mediated repair
process to remove crosslinked DNA. Other DNA damage resistant organisms
and chemoresistant cancer cells might adopt a similar strategy to
develop
resistance to DNA crosslinking agents.
Submitted by Judith Langenick [[log in to unmask]]
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Phase variation has a role in Burkholderia ambifaria niche adaptation
Ludovic Vial(1), Marie-Christine Groleau(1), Martin G Lamarche(1),
Geneviève
Filion(2), Josée Castonguay-Vanier(1), Valérie Dekimpe(1), France
Daigle(3),
Steve J Charette(2,4) and Eric Déziel(1)
1INRS-Institut Armand Frappier, Laval, Québec, Canada
2Centre de recherche de l'Institut universitaire de cardiologie et de
pneumologie de Québec (Hôpital Laval), Québec, Canada
3Department of Microbiology and Immunology, University of Montreal,
Montréal, Québec, Canada
4Département de microbiologie et de biochimie, Faculté des sciences et
de
génie, Université Laval, Québec, Canada
ISME Journal, in press
Members of the Burkholderia cepacia complex (Bcc), such as B. ambifaria,
are effective biocontrol strains, for instance, as plant growth-
promoting
bacteria; however, Bcc isolates can also cause severe respiratory
infections
in people suffering from cystic fibrosis (CF). No distinction is known
between isolates from environmental and human origins, suggesting that
the
natural environment is a potential source of infectious Bcc species.
While
investigating the presence and role of phase variation in B. ambifaria
HSJ1,
an isolate recovered from a CF patient, we identified stable variants
that
arose spontaneously irrespective of the culture conditions. Phenotypic
and
proteomic approaches revealed that the transition from wild-type to
variant
types affects the expression of several putative virulence factors. By
using
four different infection models (Drosophila melanogaster, Galleria
mellonella, macrophages and Dictyostelium discoideum), we showed that
the wild-type was more virulent than the variant. It may be noted that
the
variant showed reduced replication in a human monocyte cell line when
compared with the wild-type. On the other hand, the variant of isolate
HSJ1
was more competitive in colonizing plant roots than the wild-type.
Furthermore, we observed that only clinical B. ambifaria isolates
generated
phase variants, and that these variants showed the same phenotypes as
observed with the HSJ1 variant. Finally, we determined that
environmental
B. ambifaria isolates showed traits that were characteristic of variants
derived from clinical isolates. Our study therefore suggest that
B.ambifaria
uses phase variation to adapt to drastically different environments: the
lung of patients with CF or the rhizosphere.
Submitted by Steve Charette [[log in to unmask]]
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[End dictyNews, volume 33, number 6]
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