MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.

By M. Stucki, Julie A. Clapperton, Duaa H. Mohammad, Michael B. Yaffe, S. Smerdon, Stephen P. Jackson. Cell, 2005

1,181 citations recorded by the source corpus.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a5538ddeeb3d2b48a299f29f700bbf77b0d0728a

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In Molecular Biology

1. Stephen P. Jackson
2. J. Bartek
3. S. Polo
4. J. Lukas
5. M. Jasin
6. L. Zou
7. Alexandre Maréchal
8. Andrew N. Blackford

In Oncology

1. Stephen P. Jackson
2. J. Bartek
3. J. Lukas
4. S. Polo
5. L. Zou
6. Alexandre Maréchal
7. J. Turner
8. C. Lukas

Citations in the corpus

• Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1 (2021, background): “2 tetrapeptide incorporating pSer139, to the tandem BRCT domain at the C-terminus of MDC1 [8] (Fig.”
• ATM Activation by Oxidative Stress (2010, background): “5 syndrome protein (NBS1), part of the multifunctional complex Mre11-Rad50-Nbs1 (MRN) [22, 23].”
• Mechanism and regulation of class switch recombination. (2008, background): “Mdc1 (mediator of DNA damage checkpoint protein 1)—Mdc1 is a mediator protein that is recruited to DSBs by binding to Nbs1 and is phosphorylated by ATM (172, 173).”
• Meiotic sex chromosome inactivation (2007, positive): “MDC1 Mediator of DNA damage DNA-repair protein that interacts with H2AX at the (Stucki et al., 2005) checkpoint 1 sites of DNA DSBs. Loss of MDC1 results in impaired recruitment of DNA DSB-repair factors (e.g. ATM to DNA DSBs) and chromosome instability. uH2A Ubiquitylated histone H2A Modification…”
• Cancer epigenetics: from mechanism to therapy. (2012, background): “Proteins such as MDC1 bind at sites of double-strand breaks by tethering to gH2AX via its tandem BRCT domain (Stucki et al., 2005).”
• RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. (2009, positive): “The central coordinating factor appears to be MDC1, a large adaptor protein, which through its BRCT domains directly binds phosphorylated S139 of g-H2AX (Stucki et al., 2005) and is among the first proteins to arrive at the DSB sites (Lukas et al.”
• The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. (2009, positive): “MDC1, therefore, amplifies the ATM-dependent DNA damage response (Lou et al., 2006; Stucki et al., 2005).”
• Reading protein modifications with interaction domains (2006, background): “For example, the phosphorylation of Ser139 of histone γH2AX by the ATM (ataxia telangiectasia mutated) protein kinase following DNA damage provides an optimal binding site for the tandem BRCT domains of MDC1 (mediator of DNA-damage checkpoint protein-1), which functions as a scaffold to recruit fa”
• Repair of strand breaks by homologous recombination. (2013, background): “Its accumulation and H2AX phosphorylation (gH2AX) signal the recruitment of MDC1 (Stucki et al. 2005), which in turn recruits 53BP1 (Luijsterburg and van Attikum 2012) and then the E3 ubiquitin ligases, RNF8, RNF168, and BRCA1 (Huen et al.”
• DNA damage sensing by the ATM and ATR kinases. (2013, background): “Through its BRCT domains, Mdc1 directly binds to phosphorylated H2AX (known asgH2AX) and is required for full-sized gH2AX foci formation (Stewart et al. 2003; Lee et al. 2005; Stucki et al. 2005).”