Disruption of BRCA I function results in telomere lengthening and increased anaphase bridge formation in immortalized cell lines

BRCA1 is a tumor suppressor that functions in controlling cell growth and maintaining genomic stability. BRCA1 has also been implicated in telomere maintenance through its ability to regulate the transcription of hTERT, the catalytic subunit of telomerase, resulting in telomere shortening, and to colocalize with the telomere-binding protein TRF1. The high incidence of nonreciprocal translocations in tumors arising from BRCA1 mutation carriers and Brca1-null mice also raises the possibility that BRCA1 plays a role in telomere protection. To date, however, the consequences for telomere status of disrupting BRCA1 have not been reported. To examine the role of BRCA1 in telomere regulation, we have expressed a dominant-negative mutant of BRCA1 (trBRCA1), known to disrupt multiple functions of BRCA1, in telomerase-positive mammary epithelial cells (SVCT) and telomerase-negative ALT cells (GM847). In SVCT cells, expression of trBRCA1 resulted in an increased incidence of anaphase bridges and in an increase in telomere length, but no change in telomerase activity. In GM847 cells, trBRCA1 also increased anaphase bridge formation but did not induce any change in telomere length. BRCA1 colocalized with TRF2 in telomerase-positive cells and with a small subset of ALT-associated PML bodies (APBs) in ALT cells. Together, these results raise the possibility that BRCA1 could play a role in telomere protection and suggest a potential mechanism for one of the phenotypes of BRCA1 deficient cells. (c) 2005 Wiley-Liss, Inc.

Structural and functional characterization of the conserved salt bridge in mammalian Paneth cell alpha-defensins - Solution structures of mouse cryptdin-4 AND (E15D)-cryptdin-4

Defensins are mediators of mammalian innate immunity, and knowledge of their structure-function relationships is essential for understanding their mechanisms of action. We report here the NMR solution structures of the mouse Paneth cell α-defensin cryptdin-4 (Crp4) and a mutant (E15D)-Crp4 peptide, in which a conserved Glu15 residue was replaced by Asp. Structural analysis of the two peptides confirms the involvement of this Glu in a conserved salt bridge that is removed in the mutant because of the shortened side chain. Despite disruption of this structural feature, the peptide variant retains a well defined native fold because of a rearrangement of side chains, which result in compensating favorable interactions. Furthermore, salt bridge-deficient Crp4 mutants were tested for bactericidal effects and resistance to proteolytic degradation, and all of the variants had similar bactericidal activities and stability to proteolysis. These findings support the conclusion that the function of the conserved salt bridge in Crp4 is not linked to bactericidal activity or proteolytic stability of the mature peptide.

Trade-offs between timber production and biodiversity in rainforest plantations: Emerging issues and an ecological perspective

During the past two centuries there have been three major paradigm shifts in the management of Australian rainforests and the use of their timbers: from felling native forests towards growing plantations; from viewing forests and plantations as mainly providers of timber to viewing them as sources of multiple benefits (e.g. timber, biodiversity, carbon sequestration, catchment protection, recreation, regional economic development); and from timber plantations being developed mainly by government on public land towards those established by private citizens, companies, or joint venture arrangements, on previously-cleared freehold land. Rainforest timber plantations are increasingly established for varied reasons, and with multiple objectives. Landholders are increasingly interested in the biodiversity values of their plantations. However, there are few guidelines on the changes to plantation design and management that would augment biodiversity outcomes, or on the extent to which this might require a sacrifice of production. [Abstract extract]

Biodiversity values of timber plantations and restoration plantings for rainforest fauna in tropical and subtropical Australia

It has been suggested that timber plantations could play an important role in the conservation of biodiversity in cleared rainforest landscapes, not only because of their potential to cost-effectively reforest large areas of land, but also because they may provide habitat for rainforest plants and animals. However, this last claim is largely untested. In this study, we surveyed the occurrence of a range of animal taxa in monoculture and mixed species timber plantations and restoration plantings in tropical and subtropical Australia. We used the richness of ‘rainforest-dependent’ taxa (i.e., birds, lizards and mites associated with rainforest habitats) in reforested sites as our measure of their ‘biodiversity value’. We also examined whether the biodiversity value of reforested sites was correlated with habitat attributes, including plant species richness and vegetation structure and, further, whether biodiversity value was affected by the proximity of reforested sites to intact rainforest.

Species performance and site relationships for rainforest timber species in plantations in the humid tropics of Queensland

The performance of 32 tropical rainforest and eucalypt tree species grown in private, mixed species plantations was examined. There were two objectives: 1) to summarise the growth of species by soil and rainfall classes, 2) to investigate the degree of variability in growth rates with respect to environmental variables. Data were collected from 112 plots established in the Community Rainforest Reforestation Program (CRRP) plantations across sites in the humid tropics of central and north Queensland. Sites ranged from sea level to 1160 m above sea level, with annual rainfall from 800 mm to 4300 mm, on soils derived from basalt, metamorphic and granite parent material. Species performance was significantly related to climatic and edaphic variables but the strength of these relationships differed among taxa.