Functional Interaction Between BRCA1 and DNA Repair in Yeast May Uncover a Role of RAD50, RAD51, MRE11A, and MSH6 Somatic Variants in Cancer Development

In this study, we determined if BRCA1 partners involved in DNA double-strand break (DSB) and mismatch repair (MMR) may contribute to breast and ovarian cancer development. Taking advantage the functional conservation of DNA repair pathways between yeast and human, we expressed several BRCA1 missense variants in DNA repair yeast mutants to identify functional interaction between BRCA1 and DNA repair in BRCA1-induced genome instability. The pathogenic p.C61G, pA1708E, p.M775R, and p.I1766S, and the neutral pS1512I BRCA1 variants increased intra-chromosomal recombination in the DNA-repair proficient strain RSY6. In the mre11, rad50, rad51, and msh6 deletion strains, the BRCA1 variants p.C61G, pA1708E, p.M775R, p.I1766S, and pS1215I did not increase intra-chromosomal recombination suggesting that a functional DNA repair pathway is necessary for BRCA1 variants to determine genome instability. The pathogenic p.C61G and p.I1766S and the neutral p.N132K, p.Y179C, and p.N550H variants induced a significant increase of reversion in the msh2Δ strain; the neutral p.Y179C and the pathogenic p.I1766S variant induced gene reversion also, in the msh6Δ strain. These results imply a functional interaction between MMR and BRCA1 in modulating genome instability. We also performed a somatic mutational screening of MSH6, RAD50, MRE11A, and RAD51 genes in tumor samples from 34 patients and identified eight pathogenic or predicted pathogenic rare missense variants: four in MSH6, one in RAD50, one in MRE11A, and two in RAD51. Although we found no correlation between BRCA1 status and these somatic DNA repair variants, this study suggests that somatic missense variants in DNA repair genes may contribute to breast and ovarian tumor development

Planck intermediate results XXIV : Constraints on variations in fundamental constants

Any variation in the fundamental physical constants, more particularly in the fine structure constant, a, or in the mass of the electron, me, affects the recombination history of the Universe and cause an imprint on the cosmic microwave background angular power spectra. We show that the Planck data allow one to improve the constraint on the time variation of the fine structure constant at redshift z - 10(3) by about a factor of 5 compared to WMAP data, as well as to break the degeneracy with the Hubble constant, H-0. In addition to a, we can set a constraint on the variation in the mass of the electron, me, and in the simultaneous variation of the two constants. We examine in detail the degeneracies between fundamental constants and the cosmological parameters, in order to compare the limits obtained from Planck and WMAP and to determine the constraining power gained by including other cosmological probes. We conclude that independent time variations of the fine structure constant and of the mass of the electron are constrained by Planck to Delta alpha/alpha = (3.6 +/- 3.7) x 10(-3) and Delta m(e)/m(e) = (4 +/- 11) x 10(-3) at the 68% confidence level. We also investigate the possibility of a spatial variation of the fine structure constant. The relative amplitude of a dipolar spatial variation in a (corresponding to a gradient across our Hubble volume) is constrained to be delta alpha/alpha = (-2.4 +/- 3.7) x 10(-2).Peer reviewe

Planck Intermediate Results. XXXVI. Optical identification and redshifts of Planck SZ sources with telescopes at the Canary Islands Observatories

We present the results of approximately three years of observations of Planck Sunyaev-Zeldovich (SZ) sources with telescopes at the Canary Islands observatories as part of the general optical follow-up programme undertaken by the Planck collaboration. In total, 78 SZ sources are discussed. Deep-imaging observations were obtained for most of these sources; spectroscopic observations in either in long-slit or multi-object modes were obtained for many. We effectively used 37.5 clear nights. We found optical counterparts for 73 of the 78 candidates. This sample includes 53 spectroscopic redshift determinations, 20 of them obtained with a multi-object spectroscopic mode. The sample contains new redshifts for 27 Planck clusters that were not included in the first Planck SZ source catalogue (PSZ1).Comment: 15 pages, 14 figures, accepted for publication in A&

VizieR Online Data Catalog: Planck high-z source candidates catalog (PHZ) (Planck+, 2016)

We present in this work the Planck List of Highredshift Source Candidates (the "PHZ"), which includes 2151 sources distributed over 26% of the sky, with redshifts likely to be greater than 2. (2 data files)

VizieR Online Data Catalog: 1Jy northern AGN sample (Planck+, 2016)

The complete sample presented in this paper consists of 104 northern and equatorial radio-loud AGN. It includes all AGN with declination >=-10° that have a measured average radio flux density at 37GHz exceeding 1Jy. Most of the sample sources have been monitored at Metsahovi Radio Observatory for many years, and the brightest sources have been observed for up to 30yr. (1 data file)

VizieR Online Data Catalog: Planck Catalogue of Galactic cold clumps (PGCC) (Planck+, 2016)

The Planck Catalogue of Galactic Cold Clumps (PGCC) is a list of 13188 Galactic sources and 54 sources located in the Small and Large Magellanic Clouds. The sources have been identified in Planck data as sources colder than their environment. It has been built using the 48 months Planck data at 857, 545, and 353GHz combined with the 3THz IRAS data. (1 data file)

VizieR Online Data Catalog: Second Planck Catalogue of Compact Sources (PCCS2) (Planck+, 2016)

The Low Frequency Instrument (LFI) DPC produced the 30, 44, and 70GHz maps after the completion of eight full surveys (spanning the period 12 August 2009 to 3 August 2013). In addition, special LFI maps covering the period 1 April 2013 to 30 June 2013 were produced in order to compare the Planck flux-density scales with those of the Very Large Array and the Australia Telescope Compact Array, by performing simultaneous observations of a sample of sources over that period. The High Frequency Instrument (HFI) DPC produced the 100, 143, 217, 353, 545, and 857GHz maps after five full surveys (2009 August 12 to 2012 January 11). (16 data files)

VizieR Online Data Catalog: Planck Sunyaev-Zeldovich sources (PSZ2) (Planck+, 2016)

Three pipelines are used to detect SZ clusters: two independent implementations of the Matched Multi-Filter (MMF1 and MMF3), and PowellSnakes (PwS). The main catalogue is constructed as the union of the catalogues from the three detection methods. The completeness and reliability of the catalogues have been assessed through internal and external validation as described in section 4 of the paper. (5 data files)

Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach

Alterations in DNA repair pathways are one of the main drivers of cancer insurgence. Nevertheless, cancer cells are more susceptible to DNA damage than normal cells and they rely on specific functional repair pathways to survive. Thanks to advances in genome sequencing, we now have a better idea of which genes are mutated in specific cancers and this prompted the development of inhibitors targeting DNA repair players involved in pathways essential for cancer cells survival. Currently, the pivotal concept is that combining the inhibition of mechanisms on which cancer cells viability depends is the most promising way to treat tumorigenesis. Numerous inhibitors have been developed and for many of them, efficacy has been demonstrated either alone or in combination with chemo or radiotherapy. In this review, we will analyze the principal pathways involved in cell cycle checkpoint and DNA repair focusing on how their alterations could predispose to cancer, then we will explore the inhibitors developed or in development specifically targeting different proteins involved in each pathway, underscoring the rationale behind their usage and how their combination and/or exploitation as adjuvants to classic therapies could help in patients clinical outcome