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Nitrogen ([N.sub.2])-fixing marine cyanobacteria are an important source of fixed inorganic nitrogen that supports oceanic primary productivity and carbon dioxide removal from the atmosphere (1). A globally distributed (2,3), periodically abundant (4) [N.sub.2]-fixing (5) marine cyanobacterium, UCYN-A, was recently found to lack the oxygen-producing photosystem II complex (6) of the photosynthetic apparatus, indicating a novel metabolism, but remains uncultivated. Here we show, from metabolic reconstructions inferred from the assembly of the complete UCYN-A genome using massively parallel pyro-sequencing of paired-end reads, that UCYN-A has a photofermentative metabolism and is dependent on other organisms for essential compounds. We found that UCYN-A lacks a number of major metabolic pathways including the tricarboxylic acid cycle, but retains sufficient electron transport capacity to generate energy and reducing power from light. Unexpectedly, UCYN-A has a reduced genome (1.44 megabases) that is structurally similar to many chloroplasts and some bacteria, in that it contains inverted repeats of ribosomal RNA operons (7). The lack of biosynthetic pathways for several amino acids and purines suggests that this organism depends on other organisms, either in close association or in symbiosis, for critical nutrients. However, size fractionation experiments using natural populations have so far not provided evidence of a symbiotic association with another microorganism. The UCYN-A cyanobacterium is a paradox in evolution and adaptation to the marine environment, and is an example of the tight metabolic coupling between microorganisms in oligotrophic oceanic microbial communities., Cyanobacteria are among the most ancient and widespread photosynthetic microorganisms on the Earth, inhabiting both land and sea, and provide oxygen to the atmosphere through the water-splitting activity of photosystem [...]

The sensitivity of conventional DNA sequencing in tumor biopsies is limited by stromal contamination and by genetic heterogeneity within the cancer. Here, we show that microreactor-based pyrosequencing can detect rare cancer-associated sequence variations by independent and parallel sampling of multiple representatives of a given DNA fragment. This technology can thereby facilitate accurate molecular diagnosis of heterogeneous cancer specimens and enable patient selection for targeted cancer therapies. NOTE:: In the version of this article initially published, it should have been acknowledged that Jan F. Simons, in addition to Roman K. Thomas and Elizabeth Nickerson, contributed equally to this work. The error has been corrected in the HTML and PDF versions of the article., Author(s): Roman K Thomas [1, 2, 12]; Elizabeth Nickerson [3, 12]; Jan F Simons [3, 11, 12]; Pasi A Janne [1]; Torstein Tengs [1, 2]; Yuki Yuza [1]; Levi A [...]

Author(s): Gernot Glöckner (corresponding author) [1]; Ludwig Eichinger (corresponding author) [2]; Karol Szafranski [1]; Justin A. Pachebat [3]; Alan T. Bankier [3]; Paul H. Dear [3]; Rüdiger Lehmann [1]; Cornelia [...]

MEC1 and RAD53 are essential genes for the cell cycle and transcriptional responses to DNA damage and DNA replication blocks. Essential function of these genes has been studied. Mec1 is more important than Rad53 in response to inhibition of DNA synthesis, based on study of viable null alleles. Their lethality defects can be suppressed by greater expression of genes encoding ribonucleotide reductase. However, that is not the case for the checkpoint defects. It appears that the checkpoint pathway plays has an important role in maintaining DNA synthetic capabilities when DNA replication is stressed.

Mutants of the Saccharomyces Cerevisiae ataxia telangiectasia mutated (ATM) homolog MEC1/SAD3/ESR1 were identified that could live only if the RAD53/SAD1 checkpoint kinase was overproduced. MEC1 and a structurally related gene, TEL1, have overlapping functions in response to DNA damage and replication blocks that in mutants can be provided by overproduction of RAD53. Both MEC1 and TEL1 were found to control phosphorylation of Rad53p in response to DNA damage. These results indicate that RAD53 is a signal transducer in the DNA damage and replication checkpoint pathways and functions downstream of two members of the ATM lipid kinase family. Because several members of this pathway are conserved among eukaryotes, it is likely that a RAD53-related kinase will function downstream of the human ATM gene product and play an important role in the mammalian response to DNA damage., The ability to coordinate cell cycle transitions in response to genotoxic stress is critical to the maintenance of genomic stability. Mutations in mammalian genes that abrogate this response, such as [...]