A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers

Cyclin D1 is a component of the core cell cycle machinery. Abnormally high levels of cyclin D1 are detected in many human cancer types. To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process. We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation. These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition.     

Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase

Thiamine pyrophosphate 1 is an essential cofactor in all living systems. Its biosynthesis involves the separate syntheses of the pyrimidine 2 and thiazole 3 precursors, which are then coupled. Two biosynthetic routes to the thiamine thiazole have been identified. In prokaryotes, five enzymes act on three substrates to produce the thiazole via a complex oxidative condensation reaction, the mechanistic details of which are now well established. In contrast, only one gene product is involved in thiazole biosynthesis in eukaryotes (THI4p in Saccharomyces cerevisiae). Here we report the preparation of fully active recombinant wild-type THI4p, the identification of an iron-dependent sulphide transfer reaction from a conserved cysteine residue of the protein to a reaction intermediate and the demonstration that THI4p is a suicide enzyme undergoing only a single turnover.     

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.     

Influence of water size and type on bat captures in the lower Sonoran Desert

We compared bat use by mist-netting at 4 different types of wildlife water developments in southwestern Arizona during summer 2000 and 2001. Scaling our results by netting effort, we caught bats more frequently and observed higher species diversity at tinajas (modified natural rock pools) with larger open-water area compared with ""guzzler"" type water developments that had less open water and more obstacles to bat flight. We caught the fewest bats at guzzlers with buried concrete vault drinkers, which impede bat access and have the smallest areas of open water. Water development designs that minimize evaporative water loss by reducing the amount of open water apparently reduce use by bats in this area.     

Roost sites of the silver-haired bat ( Lasionycyeris noctivagans ) in the Black Hills, South Dakota

We investigated the roosting ecology of silver-haired bats ( Lasionycteris noctivagans ) in the Black Hills, of western South Dakota. Using radiotelemetry, we located 39 roosts, 10 of which were maternity aggregations containing 6 to 55 bats. The roosts were mostly in ponderosa pine ( Pinus ponderosa ) snags that averaged 39 cm diameter at breast height. Solitary bats preferred roosting under loose bark or in crevices in trees, regularly moving among trees. All maternity aggregations were found in tree cavities, primarily those created by woodpeckers. Roost trees were located in patches of forest with relatively high snag densities, about 21 snags/ha. This study suggests that snags play an important role in maintain silver-haired bat populations in ponderosa pine ecosystems.     

Efficacy of using passive integrated transponder technology to track individual shorthead sculpins

We evaluated the feasibility of using passive integrated transponder (PIT) tags to mark and track individual shorthead sculpins ( Cottus confusus ). We implanted PIT tags in 80 shorthead sculpins in 2 size categories (60–80 mm and 81–106 mm total length) and in 1 of 2 locations (subcutaneous along the spinous dorsal fin or in the body cavity). We evaluated tag retention, sculpin survival, and net-avoidance behavior for 29 days. We observed no mortality directly attributable to PIT-tag injection at either tagging location. We observed a 38.8% loss rate of dorsal tags and a 2.5% loss rate of body-cavity tags. No change in net-avoidance behavior was observed. We released 97 PIT-tagged sculpins into an artificial stream and monitored them with 3 stationary and 1 portable antenna. Sixty sculpins were detected at least once, and 18 sculpins were detected multiple times with the portable antenna. These results indicate that PIT-tagging within the body cavity is a feasible method for marking and tracking individual shorthead sculpins.     

Fire history of Paunsaugunt Plateau in southern Utah

A fire history of the Pausaugunt Plateau in southern Utah was developed using dendrochronological methods. Fire frequencies of individual ponderosa pine trees from three sites on the plateau varied from 19.5 to 47 years. Composite fire intervals for the three sites ranged from 15.2 to 18.4 years. The last recorded fires in these study areas occurred in 1892, 1902, and 1911, corresponding to the initiation of fire suppression policies in the West. The absence of fire since 1911 may be contributing to a recently documented decrease in ponderosa pine regeneration within the high-elevation, mixed-coniferous forests of the Paunsaugunt Plateau.