The Impact of Contaminated RR Lyrae/Globular Cluster Photometry on the Distance Scale

RR Lyrae variables and the stellar constituents of globular clusters are employed to establish the cosmic distance scale and age of the universe. However, photometry for RR Lyrae variables in the globular clusters M3, M15, M54, M92, NGC2419, and NGC6441 exhibit a dependence on the clustercentric distance. For example, variables and stars positioned near the crowded high-surface brightness cores of the clusters may suffer from photometric contamination, which invariably affects a suite of inferred parameters (e.g., distance, color excess, absolute magnitude, etc.). The impetus for this study is to mitigate the propagation of systematic uncertainties by increasing awareness of the pernicious impact of contaminated and radial-dependent photometry.Comment: To appear in ApJ

Stress, specificity and the NEDD8 proteome

Comment on: Leidecker O, et al. Cell Cycle 2012; 1142–5

Targeting ATM pathway for therapeutic intervention in cancer

The Ataxia Telangiectasia Mutated gene encodes the ATM protein, a key element in the DNA damage response (DDR) signalling pathway responsible for maintaining genomic integrity within the cell. The ATM protein belongs to a family of large protein kinases containing the phosphatidylinositol-3 catalytic domain, including ATM, ATR and PI3K. ATM provides the crucial link between DNA damage, cell cycle progression and cell death by first sensing double stranded DNA breaks and subsequently phosphorylating and activating other downstream proteins functioning in DNA damage repair, cell cycle arrest and apoptotic pathways,. Mammalian cells are constantly challenged by genotoxic agents from a variety of sources and therefore require a robust sensing and repair mechanism to maintain DNA integrity or activate alternative cell fate pathways. This review covers the role of ATM in DDR signalling and describes the interaction of the ATM kinase with other proteins in order to fulfil its various functions. Special emphasis is given to how the growing knowledge of the DDR can help identify drug targets for cancer therapy, thus providing a rationale for exploiting the ATM pathway in anticancer drug development. Moreover, we discuss how a network modelling approach can be used to identify and characterise ATM inhibitors and predict their therapeutic potential

The z=0.0912 and z=0.2212 Damped Lyman Alpha Galaxies Along the Sight-Line Toward the Quasar OI 363

New optical and infrared observations along the sight-line toward the quasar OI 363 (0738+313) are presented and discussed. Excluding systems which lack confirming UV spectroscopic observations of the actual Lyman alpha line, this sight-line presently contains the two lowest-redshift classical damped Lyman alpha (DLA) quasar absorption line systems known (i.e. with N(HI) \ge 2 x 10^{20} atoms cm^{-2}), one at z(abs)=0.0912 and the other at z(abs)=0.2212. The z=0.09 DLA galaxy appears to be an extended low surface brightness galaxy which is easily visible only in infrared images and shows rich morphological structure. Subtraction of the quasar nuclear and host light yields L_K \approx 0.08L_K* at z=0.09. The impact parameter between the galaxy and quasar sight-line is very small, b<3.6 kpc (<2 arcsec), which makes measurements difficult. The z=0.22 DLA galaxy is an early-type dwarf with a K-band luminosity of L_K \approx 0.1L_K* at impact parameter b=20 kpc. In general, these results serve to support mounting evidence that DLA galaxies are drawn from a wide variety of gas-rich galaxy types. (Abridged)Comment: 27 pages, 6 figures, 2 in color. Submitted to Ap

PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain

The eukaryotic polymerase processivity factor, PCNA, interacts with cell cycle regulatory proteins such as p21^(WAF1/Cip1) and Gadd45, as well as with proteins involved in the mechanics of DNA repair and replication. A conserved PCNA-binding motif is found in a subset of PCNA-interacting proteins, including p21, suggesting that the regulation of these interactions is important for the co-ordination of DNA replication and repair. We have identified several classes of protein which bind to Drosophila PCNA. Two of these proteins contain the consensus PCNA-binding domain: one is the Dacapo protein, a Drosophila homologue of p21^(WAF1/Cip1), and the second is the transposase encoded by the Pogo DNA transposon. A conserved PCNA-binding domain is also present in a human relative of Pogo, named Tigger, suggesting that this domain has a functional role in this class of transposable element. This raises interesting possibilities for a novel method of transposition in which the transposase might be targeted to replicating DNA. Finally, we have investigated the use of this conserved PCNAbinding domain as a predictor of PCNA-binding capacity

PCNA binding proteins in Drosophila melanogaster : the analysis of a conserved PCNA binding domain

The eukaryotic polymerase processivity factor, PCNA, interacts with cell cycle regulatory proteins such as p21^(WAF1/Cip1) and Gadd45, as well as with proteins involved in the mechanics of DNA repair and replication. A conserved PCNA-binding motif is found in a subset of PCNA-interacting proteins, including p21, suggesting that the regulation of these interactions is important for the co-ordination of DNA replication and repair. We have identified several classes of protein which bind to Drosophila PCNA. Two of these proteins contain the consensus PCNA-binding domain: one is the Dacapo protein, a Drosophila homologue of p21^(WAF1/Cip1), and the second is the transposase encoded by the Pogo DNA transposon. A conserved PCNA-binding domain is also present in a human relative of Pogo, named Tigger, suggesting that this domain has a functional role in this class of transposable element. This raises interesting possibilities for a novel method of transposition in which the transposase might be targeted to replicating DNA. Finally, we have investigated the use of this conserved PCNAbinding domain as a predictor of PCNA-binding capacity

Differences in the ubiquitination of p53 by Mdm2 and the HPV protein E6

AbstractThe human papillomavirus (HPV) protein E6 can promote the ubiquitination of the p53 tumour suppressor in vitro, providing an explanation for the ability of E6 to induce p53 degradation in vivo and contribute to the potential tumorigenic effect of the virus. Instead, in non-infected cells, p53 levels are primarily destabilised by the ubiquitin E3 ligase activity of the Mdm2 protein. Here we have compared the effects of E6 and Mdm2 on p53 ubiquitination in vivo. We show that whereas in the presence of Mdm2 proteasome inhibitors induce the accumulation of ubiquitinated forms of p53, this does not occur in the presence of E6. Accordingly, we confirm that the effect of E6 and p53 is independent of the six C-terminal lysine residues in p53, which have previously been described to play an important role for effective ubiquitination and degradation of 53 mediated by Mdm2. We also show that other yet unidentified residues in p53 are also susceptible to ubiquitination. These results indicate that E6 does not induce ubiquitination of p53 in the same way as Mdm2 in order to promote its degradation, suggesting important differences between the Mdm2 and E6 effects on p53 degradation