A novel ubiquitin ligase is deficient in Fanconi anemia

Fanconi anemia is a recessively inherited disease characterized by congenital defects, bone marrow failure and cancer susceptibility. Cells from individuals with Fanconi anemia are highly sensitive to DNA-crosslinking drugs, such as mitomycin C (MMC). Fanconi anemia proteins function in a DNA damage response pathway involving breast cancer susceptibility gene products, BRCA1 and BRCA2 (refs. 1,2). A key step in this pathway is monoubiquitination of FANCD2, resulting in the redistribution of FANCD2 to nuclear foci containing BRCA1 (ref. 3). The underlying mechanism is unclear because the five Fanconi anemia proteins known to be required for this ubiquitination have no recognizable ubiquitin ligase motifs. Here we report a new component of a Fanconi anemia protein complex, called PHF9, which possesses E3 ubiquitin ligase activity in vitro and is essential for FANCD2 monoubiquitination in vivo. Because PHF9 is defective in a cell line derived from an individual with Fanconi anemia, we conclude that PHF9 (also called FANCL) represents a novel Fanconi anemia complementation group (FA-L). Our data suggest that PHF9 has a crucial role in the Fanconi anemia pathway as the likely catalytic subunit required for monoubiquitination of FANCD2.     

Ecological and genetic spatial structuring in the Canadian lynx

The Canadian lynx, distributed all across the northern part of North America, is well known for its regular population cycles-cycles that have different underlying structures in different parts of Canada. Using both nuclear and mitochondrial DNA markers, we report here a close resemblance between the earlier observed spatial ecological structuring of the Canadian lynx and its spatial genetic structuring. Specifically, we demonstrate that the Rocky Mountains represent a barrier to gene flow in western Canada, and, somewhat surprisingly, we detect the presence of a geographically invisible barrier south of Hudson Bay (coinciding with the separation between the ecological Continental and Atlantic regions). No evidence for isolation in different glacial refugia within North America was found. We suggest that ecological factors underlying the spatial dynamic structuring also strongly influence the genetic structuring of the Canadian lynx.     

Self-organization of supramolecular helical dendrimers into complex electronic materials

The discovery of electrically conducting organic crystals and polymers has widened the range of potential optoelectronic materials, provided these exhibit sufficiently high charge carrier mobilities and are easy to make and process. Organic single crystals have high charge carrier mobilities but are usually impractical, whereas polymers have good processability but low mobilities. Liquid crystals exhibit mobilities approaching those of single crystals and are suitable for applications, but demanding fabrication and processing methods limit their use. Here we show that the self-assembly of fluorinated tapered dendrons can drive the formation of supramolecular liquid crystals with promising optoelectronic properties from a wide range of organic materials. We find that attaching conducting organic donor or acceptor groups to the apex of the dendrons leads to supramolecular nanometre-scale columns that contain in their cores pi-stacks of donors, acceptors or donor-acceptor complexes exhibiting high charge carrier mobilities. When we use functionalized dendrons and amorphous polymers carrying compatible side groups, these co-assemble so that the polymer is incorporated in the centre of the columns through donor-acceptor interactions and exhibits enhanced charge carrier mobilities. We anticipate that this simple and versatile strategy for producing conductive pi-stacks of aromatic groups, surrounded by helical dendrons, will lead to a new class of supramolecular materials suitable for electronic and optoelectronic applications.     

Detecting recent positive selection in the human genome from haplotype structure

The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.