ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses.

Genotoxic stress triggers the activation of checkpoints that delay cell-cycle progression to allow for DNA repair. Studies in fission yeast implicate members of the Rad family of checkpoint proteins, which includes Rad17, Rad1, Rad9 and Hus1, as key early-response elements during the activation of both the DNA damage and replication checkpoints. Here we demonstrate a direct regulatory linkage between the human Rad17 homologue (hRad17) and the checkpoint kinases, ATM and ATR. Treatment of human cells with genotoxic agents induced ATM/ATR-dependent phosphorylation of hRad17 at Ser 635 and Ser 645. Overexpression of a hRad17 mutant (hRad17AA) bearing Ala substitutions at both phosphorylation sites abrogated the DNA-damage-induced G2 checkpoint, and sensitized human fibroblasts to genotoxic stress. In contrast to wild-type hRad17, the hRad17AA mutant showed no ionizing-radiation-inducible association with hRad1, a component of the hRad1-hRad9-hHus1 checkpoint complex. These findings demonstrate that ATR/ATM-dependent phosphorylation of hRad17 is a critical early event during checkpoint signalling in DNA-damaged cells.     

Structure of rat atrial natriuretic factor precursor deduced from cDNA sequence

The atrium of the heart contains peptides, termed atrial natriuretic factors ( ANFs ), diuretic and smooth-muscle-relaxing activities. In view of its potent effects on salt metabolism in the kidney and on vascular smooth muscle, ANF is considered to play an important part in the control of fluid volume and vascular function. Several different ANF peptides varying in size have been isolated and their amino acid sequences determined. Analysis of the sequences of the peptides suggests that they are derived by proteolysis from the same precursor. To examine this hypothesis, we have cloned cDNAs of the ANF precursor using rat atrial mRNA, determined its nucleotide sequence and deduced its amino acid sequence. The ANF precursor consists of 152 amino acid residues including a putative signal peptide sequence. This sequence contains the amino acid sequences of all the ANF peptides reported to date.     

A socially enforced signal of quality in a paper wasp

Organisms use signals of quality to communicate information about aspects of their relative phenotypic and genetic constitution. Badges of status are a subset of signals of quality that reveal information about an individual's size and dominance. In general, signals of quality require high and differential costs to remain honest (that is, prevent low-quality cheaters from exploiting any fitness benefits associated with communicating high quality). The theoretically required costs for badges of status remain controversial because the development (or 'production') of such signals often seems to be relatively cost-free. One important hypothesis is that such signals impose social (or 'maintenance') costs incurred through repeated agonistic interactions with other individuals. However, convincing empirical evidence for social costs remains elusive. Here we report social costs in a previously undescribed badge of status: the highly variable black facial patterns of female paper wasps, Polistes dominulus. Facial patterns strongly predict body size and social dominance. Moreover, in staged contests between pairs of unfamiliar wasps, subordinate wasps with experimentally altered facial features ('cheaters') received considerably more aggression from the dominant than did sham controls, indicating that facial patterns are signals and that dishonest signalling imposes social costs.