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DNA mismatch repair is an essential safeguard of genomic integrity by removing base mispairings that may arise from DNA polymerase errors or from homologous recombination between DNA strands. In Escherichia coli , the MutS enzyme recognizes mismatches and initiates repair. MutS has an intrinsic ATPase activity crucial for its function, but which is poorly understood. We show here that within the MutS homodimer, the two chemically identical ATPase sites have different affinities for ADP, and the two sites alternate in ATP hydrolysis. A single residue, Arg697, located at the interface of the two ATPase domains, controls the asymmetry. When mutated, the asymmetry is lost and mismatch repair in vivo is impaired. We propose that asymmetry of the ATPase domains is an essential feature of mismatch repair that controls the timing of the different steps in the repair cascade.

DNA mismatch repair ensures genomic integrity on DNA replication. Recognition of a DNA mismatch by a dimeric MutS protein initiates a cascade of reactions and results in repair of the newly synthesized strand; however, details of the molecular mechanism remain controversial. Here we present the crystal structure at 2.2 Å of MutS from Escherichia coli bound to a G·T mismatch. The two MutS monomers have different conformations and form a heterodimer at the structural level. Only one monomer recognizes the mismatch specifically and has ADP bound. Mismatch recognition occurs by extensive minor groove interactions causing unusual base pairing and kinking of the DNA. Nonspecific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. The interleaved nucleotide-binding sites are located far from the DNA. Mutations in human MutSα (MSH2/MSH6) that lead to hereditary predisposition for cancer, such as hereditary non-polyposis colorectal cancer, can be mapped to this crystal structure.

Candidate pre-main-sequence stars were observed in the bar of the Large Magellanic Cloud during the search for dark matter in the galactic halo. Seven blue stars of apparent visual magnitude 15 to 17 had irregular photometric variations and hydrogen emission lines in their optical spectra, which suggested that these stars are pre-main-sequence stars of about 10 solar masses. These stars are slightly more massive and definitely more luminous than are Herbig AeBe pre-main-sequence stars in our own galaxy. Continued observations of these very young stars from another galaxy, which are probably at the pre-hydrogen-burning stage, should provide important clues about early stages of star formation.

The enigmatic object η Carinae is believed to represent an important, but short-lived, unstable phase in the life of the most massive stars, occurring shortly before they explode as supernovae or collapse directly to black holes. The putative binary 1 , 2 system believed to constitute η Carinae survived an outburst in the previous century that lasted 20 years; and which created a nebula with pronounced bipolar lobes that together contain about 2.5 solar masses of material. The nebula also exhibits an equatorial ‘waist’ containing about 0.5 solar masses 3 . The physical mechanisms responsible for the outburst and the bipolar geometry are not understood. Here we report infrared observations (spectroscopy and imaging) that reveal the presence of about 15 solar masses of material, located in an equatorial torus. The massive torus may have been created through highly non-conservative mass transfer, which removed the entire envelope of one of the stars, leaving an unstable core that erupted in the nineteenth century. The collision of the erupted material with the pre-existing torus provides a natural explanation for the bipolar shape of the nebula.

Star clusters are found in all sorts of environments, and their formation and evolution is inextricably linked to the star-formation process. Their eventual destruction can result from a number of factors at different times, but the process can be investigated as a whole through the study of cluster age distributions. Observations of populous cluster samples reveal a distribution following a power law of index approximately −1. In this work, we use M33 as a test case to examine the age distribution of an archetypal cluster population and show that it is, in fact, the evolving shape of the mass detection limit that defines this trend. That is to say, any magnitude-limited sample will appear to follow a dN/dτ = τ−1 relation, while cutting the sample according to mass gives rise to a composite structure, perhaps implying a dependence of the cluster disruption process on mass. In the context of this framework, we examine different models of cluster disruption from both theoretical and observational perspectives.

DNA mismatch repair ensures genomic integrity on DNA replication. Recognition of a DNA mismatch by a dimeric MutS protein initiates a cascade of reactions and results in repair of the newly synthesized strand; however, details of the molecular mechanism remain controversial. Here we present the crystal structure of 2.2 angstrom resolution of MutS from Escherichia coli bound to a G times T mismatch. The two MutS monomers have different conformations and form a heterodimer at the structural level. Only one monomer recognizes the mismatch specifically and has ADP bound. Mismatch recognition occurs by extensive minor groove interactions causing unusual base pairing and kinking of the DNA. Nonspecific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. The interleaved nucleotide-binding sites are located far from the DNA. Mutations in human MutS alpha (MSH2/MSH6) that lead to hereditary predisposition for cancer, such as hereditary non-polyposis colorectal cancer, can be mapped to this crystal structure.

DNA mismatch repair ensures genomic integrity on DNA replication. Recognition of a DNA mismatch by a dimeric MutS protein initiates a cascade of reactions and results in repair of the newly synthesized strand; however, details of the molecular mechanism remain controversial. Here we present the crystal structure at 2.2 A of MutS from Escherichia coli bound to a G x T mismatch. The two MutS monomers have different conformations and form a heterodimer at the structural level. Only one monomer recognizes the mismatch specifically and has ADP bound. Mismatch recognition occurs by extensive minor groove interactions causing unusual base pairing and kinking of the DNA. Nonspecific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. The interleaved nucleotide-binding sites are located far from the DNA. Mutations in human MutS alpha (MSH2/MSH6) that lead to hereditary predisposition for cancer, such as hereditary non-polyposis colorectal cancer, can be mapped to this crystal structure.

Globular clusters (GCs), once thought to be well approximated as simple stellar populations (i.e. all stars having the same age and chemical abundance), are now known to host a variety of anomalies, such as multiple discrete (or spreads in) populations in colour-magnitude diagrams and abundance variations in light elements (e.g., Na, O, Al). Multiple models have been put forward to explain the observed anomalies, although all have serious shortcomings (e.g., requiring a non-standard initial mass function of stars and GCs to have been initially 10-100 times more massive than observed today). These models also do not agree with observations of massive stellar clusters forming today, which do not display significant age spreads nor have gas/dust within the cluster. Here we present a model for the formation of GCs, where low mass pre-main sequence (PMS) stars accrete enriched material released from interacting massive binary and rapidly rotating stars onto their circumstellar discs, and ultimately onto the young stars. As was shown in previous studies, the accreted material matches the unusual abundances and patterns observed in GCs. The proposed model does not require multiple generations of star-formation, conforms to known properties of massive clusters forming today, and solves the \"mass budget problem\" without requiring GCs to have been significantly more massive at birth. Potential caveats to the model as well as model predictions are discussed.

Evolutionary synthesis models are the prime method to construct models of stellar populations, and to derive physical parameters from observations. One of the assumptions for such models so far has been the time-independence of the stellar mass function. However, dynamical simulations of star clusters in tidal fields have shown the mass function to change due to the preferential removal of low-mass stars from clusters. Here we combine the results from dynamical simulations of star clusters in tidal fields with our evolutionary synthesis code GALEV to extend the models by a new dimension: the total cluster disruption time. We reanalyse the mass function evolution found in N-body simulations of star clusters in tidal fields, parametrise it as a function of age and total cluster disruption time and use this parametrisation to compute GALEV models as a function of age, metallicity and the total cluster disruption time. We study the impact of cluster dissolution on the colour (generally, they become redder) and magnitude (they become fainter) evolution of star clusters, their mass-to-light ratios (off by a factor of ~2 -- 4 from standard predictions), and quantify the effect on the cluster age determination from integrated photometry (in most cases, clusters appear to be older than they are, between 20 and 200%). By comparing our model results with observed M/L ratios for old compact objects in the mass range 10^4.5 -- 10^8 Msun, we find a strong discrepancy for objects more massive than 10^7 Msun (higher M/L). This could be either caused by differences in the underlying stellar mass function or be an indication for the presence of dark matter in these objects. Less massive objects are well represented by the models. The models for a range of total cluster disruption times are available online. (shortened)

Star clusters are found in all sorts of environments and their formation and evolution is inextricably linked to the star formation process. Their eventual destruction can result from a number of factors at different times, but the process can be investigated as a whole through the study of the cluster age distribution. Observations of populous cluster samples reveal a distribution following a power law of index approximately -1. In this work we use M33 as a test case to examine the age distribution of an archetypal cluster population and show that it is in fact the evolving shape of the mass detection limit that defines this trend. That is to say, any magnitude-limited sample will appear to follow a dN/dt=1/t, while cutting the sample according to mass gives rise to a composite structure, perhaps implying a dependence of the cluster disruption process on mass. In the context of this framework, we examine different models of cluster disruption from both theoretical and observational standpoints.