Williams, E. S. et al. DNA double-strand breaks are not sufficient to initiate recruitment of TRF2. Nature Genet. 39, 696-698

Department of Cell Biology, Erasmus University Rotterdam, Rotterdam, South Holland, Netherlands
Nature Genetics (Impact Factor: 29.35). 07/2007; 39(6):696-8; author reply 698-9. DOI: 10.1038/ng0607-696
Source: PubMed
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Available from: Martijn S Luijsterburg
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    • "DNA photosensitizers induce numerous lesions within the DNA including base lesions, SSBs and DSBs (Table 1) [2,3,11,36–39] at the same time minimizing the contribution of UV-type damage. Not only the presence of photosensitisers but also the laser power may greatly influence the findings [40] as discussed below. The caveat of using photosensitizers is that the repair of DNA lesions may be hindered by the presence of the DNA interchelator and the exact mode of action of the photosensitizers, following excitation, electron transfer etc., has yet to be fully characterized. "
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    ABSTRACT: The formation of DNA lesions poses a constant threat to cellular stability. Repair of endogenously and exogenously produced lesions has therefore been extensively studied, although the spatiotemporal dynamics of the repair processes has yet to be fully understood. One of the most recent advances to study the kinetics of DNA repair has been the development of laser microbeams to induce and visualize recruitment and loss of repair proteins to base damage in live mammalian cells. However, a number of studies have produced contradictory results that are likely caused by the different laser systems used reflecting in part the wavelength dependence of the damage induced. Additionally, the repair kinetics of laser microbeam induced DNA lesions have generally lacked consideration of the structural and chemical complexity of the DNA damage sites, which are known to greatly influence their reparability. In this review, we highlight the key considerations when embarking on laser microbeam experiments and interpreting the real time data from laser microbeam irradiations. We compare the repair kinetics from live cell imaging with biochemical and direct quantitative cellular measurements for DNA repair.
    Full-text · Article · May 2013 · Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
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    • "A limitation of these laser-based methods is that, besides DSBs, they also give rise to a wide spectrum of other DNA lesions, including cyclobutane pyrimidine dimers, 6,4 pyrimidine-pyrimidones and ssDNA breaks (Bekker-Jensen et al., 2006; Dinant et al., 2007; Kong et al., 2009). Furthermore, structural changes in the DNA that are caused by intercalation of Hoechst dye may lead to nonphysiological DDR (Dinant et al., 2007; Kong et al., 2009; Williams et al., 2007a). UV-A treatment, if applied at high power, can also elicit aberrant cellular responses by inducing protein damage or protein– protein and protein–DNA crosslinks. "
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    ABSTRACT: Polycomb group (PcG) genes encode chromatin modifiers that are involved in the maintenance of cell identity and in proliferation, processes that are often deregulated in cancer. Interestingly, besides a role in epigenetic gene silencing, recent studies have begun to uncover a function for PcG proteins in the cellular response to DNA damage. In particular, PcG proteins have been shown to accumulate at sites of DNA double-strand breaks (DSBs). Several signaling pathways contribute to the recruitment of PcG proteins to DSBs, where they catalyze the ubiquitylation of histone H2A. The relevance of these findings is supported by the fact that loss of PcG genes decreases the efficiency of cells to repair DSBs and renders them sensitive to ionizing radiation. The recruitment of PcG proteins to DNA breaks suggests that they have a function in coordinating gene silencing and DNA repair at the chromatin flanking DNA lesions. In this Commentary, we discuss the current knowledge of the mechanisms that allow PcG proteins to exert their positive functions in genome maintenance.
    Full-text · Article · Sep 2012 · Journal of Cell Science
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    • "– Recognizes ds/ss DNA junctions [203], Holliday junctions [83] [149], G4 structures [53], high energy laser DNA damages [204] [205] and positively supercoiled DNA [159] – Forms t-loops [7,78] – Binds TERRA RNA [72] – Protects Holliday junctions from resolvases cleavage and from Werner-mediated resolution [83] [150] – Condenses DNA [63] – Introduction of positive supercoils around itself [63] – Binds better positively supercoiled than relaxed or negatively supercoiled DNA [159] – Stimulates ssDNA invasion into duplex DNA [63] [80] – Regulates the enzymatic activities of Werner [192] [206], MUS81 [207], DNA polymerase beta [208], and Apollo [159] TIN2, RAP1, POT1, Apollo, ATM, MRN complex, WRN, BLM, Ku70, ORC1 and PARP1, 2 [195], ERCC1/XPF [209], Topoisomerase III [210], FEN1 and DNA polymerase beta [208], SLX4 [211] [212], REST [213], PNUTS and MCPH1 [214], MUS81/EME1 [207] – Telomere protection [77] – Replication of the EB virus episome [215] [216] and of telomeres [159] – Neuronal gene silencing [213] – Global repair? [204] Vertebrate RAP1 Repressor activator protein 1 – ScRap1 homolog contains a Myb-like (pdb 1FEX), a BRCT and a RCT domain – Does not bind DNA – Inhibits NHEJ-mediated ligation in vitro [217– 219] TRF2 [141], RAD50/MRE11 and KU86 [220], IKKs [221] – Telomere length regulation [220] [222] – Inhibition of NHEJ in human cells [219] – Inhibition of T-SCE in mice [223] – Participates in subtelomeric silencing and transcriptional regulation in mice [224] – Regulates NFjB-dependent gene expression [221] "
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    ABSTRACT: A major issue in telomere research is to understand how the integrity of chromosome ends is controlled. Although several nucleoprotein complexes have been described at the telomeres of different organisms, it is still unclear how they confer a structural identity to chromosome ends in order to mask them from DNA repair and to ensure their proper replication. In this review, we describe how telomeric nucleoprotein complexes are structured, comparing different organisms and trying to link these structures to telomere biology. It emerges that telomeres are formed by a complex and specific network of interactions between DNA, RNA and proteins. The fact that these interactions and associated activities are reinforcing each other might help to guaranty the robustness of telomeric functions across the cell cycle and in the event of cellular perturbations. We propose that telomeric nucleoprotein complexes orient cell fate through dynamic transitions in their structures and their organization.
    Full-text · Article · Sep 2010 · FEBS letters
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