Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia

The evolutionarily conserved SLX4 protein, a key regulator of nucleases, is critical for DNA damage response. SLX4 nuclease complexes mediate repair during replication and can also resolve Holliday junctions formed during homologous recombination. Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia. Btbd12-deficient animals are born at sub-Mendelian ratios, have greatly reduced fertility, are developmentally compromised and are prone to blood cytopenias. Btbd12(-/-) cells prematurely senesce, spontaneously accumulate damaged chromosomes and are particularly sensitive to DNA crosslinking agents. Genetic complementation reveals a crucial requirement for Btbd12 (also known as Slx4) to interact with the structure-specific endonuclease Xpf-Ercc1 to promote crosslink repair. The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway.     

Irregular tropical glacier retreat over the Holocene epoch driven by progressive warming

The causes and timing of tropical glacier fluctuations during the Holocene epoch (10,000 years ago to present) are poorly understood. Yet constraining their sensitivity to changes in climate is important, as these glaciers are both sensitive indicators of climate change and serve as water reservoirs for highland regions. Studies have so far documented extra-tropical glacier fluctuations, but in the tropics, glacier-climate relationships are insufficiently understood. Here we present a (10)Be chronology for the past 11,000?years (11?kyr), using 57 moraines from the Bolivian Telata glacier (in the Cordillera Real mountain range). This chronology indicates that Telata glacier retreated irregularly. A rapid and strong melting from the maximum extent occurred from 10.8?±?0.9 to 8.5?±?0.4?kyr ago, followed by a slower retreat until the Little Ice Age, about 200 years ago. A dramatic increase in the rate of retreat occurred over the twentieth century. A glacier-climate model indicates that, relative to modern climate, annual mean temperature for the Telata glacier region was -3.3?±?0.8 °C cooler at 11?kyr ago and remained -2.1?±?0.8 °C cooler until the end of the Little Ice Age. We suggest that long-term warming of the eastern tropical Pacific and increased atmospheric temperature in response to enhanced austral summer insolation were the main drivers for the long-term Holocene retreat of glaciers in the southern tropics.     

Persistence of full glacial conditions in the central Pacific until 15,000 years ago

The magnitude of atmospheric cooling during the Last Glacial Maximum and the timing of the transition into the current interglacial period remain poorly constrained in tropical regions, partly because of a lack of suitable climate records. Glacial moraines provide a method of reconstructing past temperatures, but they are relatively rare in the tropics. Here we present a reconstruction of atmospheric temperatures in the central Pacific during the last deglaciation on the basis of cosmogenic 3He ages of moraines and numerical modelling of the ice cap on Mauna Kea volcano, Hawaii--the only highland in the central Pacific on which moraines that formed during the last glacial period are preserved. Our reconstruction indicates that the Last Glacial Maximum occurred between 19,000 and 16,000 years ago in this region and that temperatures at high elevations were about 7 degrees C lower than today during this interval. Glacial retreat began about 16,000 years ago, but temperatures were still about 6.5 degrees C lower than today until 15,000 years ago. When combined with estimates of sea surface temperatures in the central Pacific Ocean, our reconstruction indicates that the lapse rate during the Last Glacial Maximum was higher than at present, which is consistent with the proposal that the atmosphere was drier at that time. Furthermore, the persistence of full glacial conditions until 15,000 years ago is consistent with the relatively late and abrupt transition to warmer temperatures in Greenland, indicating that there may have been an atmospheric teleconnection between the central Pacific and North Atlantic regions during the last deglaciation.