Sandbox Reserved 1098

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=== The mechanism ===
=== The mechanism ===
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As said previously, poly(ADP-ribosylation) is an important post-translational modification for DNA repair. The mechanism behind this repair relies on several factors. At first, the Poly (ADP-ribose) polymerase (PARP), more specifically the subtype PARP1, will recognize and will bind to the single-strand break. It will then autophosphorylate due to NAD+ and form PAR chains. These will then recruit other repair proteins to the site <ref>DOI: 10.1021/acs.jmedchem.8b01407</ref>. The role of PARG is the hydrolyzation of specific ribose-ribose bonds present in PAR which leads to its degradation and stoping the repair cycle <ref>DOI: 10.1021/acs.jmedchem.8b01407</ref>. This degradation is important because without PARG the repair cycle cannot be completed <ref>PMID: 17548475</ref> due partially to the still present PARP on the previously damaged site maintained by the non-degraded PAR <ref>PMID: 16140981</ref>.
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As said previously, poly(ADP-ribosylation) is an important post-translational modification for DNA repair. The mechanism behind this repair relies on several factors. At first, the Poly (ADP-ribose) polymerase (PARP), more specifically the subtype PARP1, will recognize and will bind to the single-strand break. It will then autophosphorylate due to NAD+ and form PAR chains. These will then recruit other repair proteins to the site. The role of PARG is the hydrolyzation of specific ribose-ribose bonds present in PAR which leads to its degradation and stoping the repair cycle <ref>DOI: 10.1021/acs.jmedchem.8b01407</ref>. This degradation is important because without PARG the repair cycle cannot be completed <ref>PMID: 17548475</ref> due partially to the still present PARP on the previously damaged site maintained by the non-degraded PAR <ref>PMID: 16140981</ref>.

Revision as of 17:47, 29 December 2019

This Sandbox is Reserved from 25/11/2019, through 30/9/2020 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1091 through Sandbox Reserved 1115.
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References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ Oberle C, Blattner C. Regulation of the DNA Damage Response to DSBs by Post-Translational Modifications. Curr Genomics. 2010 May;11(3):184-98. doi: 10.2174/138920210791110979. PMID:21037856 doi:http://dx.doi.org/10.2174/138920210791110979
  4. ↑ Waszkowycz B, Smith KM, McGonagle AE, Jordan AM, Acton B, Fairweather EE, Griffiths LA, Hamilton NM, Hamilton NS, Hitchin JR, Hutton CP, James DI, Jones CD, Jones S, Mould DP, Small HF, Stowell AIJ, Tucker JA, Waddell ID, Ogilvie DJ. Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides. J Med Chem. 2018 Dec 13;61(23):10767-10792. doi: 10.1021/acs.jmedchem.8b01407., Epub 2018 Nov 19. PMID:30403352 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01407
  5. ↑ James DI, Smith KM, Jordan AM, Fairweather EE, Griffiths LA, Hamilton NS, Hitchin JR, Hutton CP, Jones S, Kelly P, McGonagle AE, Small H, Stowell AI, Tucker J, Waddell ID, Waszkowycz B, Ogilvie DJ. First-in-Class Chemical Probes against Poly(ADP-ribose) Glycohydrolase (PARG) Inhibit DNA Repair with Differential Pharmacology to Olaparib. ACS Chem Biol. 2016 Oct 12. PMID:27689388 doi:http://dx.doi.org/10.1021/acschembio.6b00609
  6. ↑ Waszkowycz B, Smith KM, McGonagle AE, Jordan AM, Acton B, Fairweather EE, Griffiths LA, Hamilton NM, Hamilton NS, Hitchin JR, Hutton CP, James DI, Jones CD, Jones S, Mould DP, Small HF, Stowell AIJ, Tucker JA, Waddell ID, Ogilvie DJ. Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides. J Med Chem. 2018 Dec 13;61(23):10767-10792. doi: 10.1021/acs.jmedchem.8b01407., Epub 2018 Nov 19. PMID:30403352 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01407
  7. ↑ Fisher AE, Hochegger H, Takeda S, Caldecott KW. Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase. Mol Cell Biol. 2007 Aug;27(15):5597-605. doi: 10.1128/MCB.02248-06. Epub 2007 Jun, 4. PMID:17548475 doi:http://dx.doi.org/10.1128/MCB.02248-06
  8. ↑ Kim MY, Zhang T, Kraus WL. Poly(ADP-ribosyl)ation by PARP-1: 'PAR-laying' NAD+ into a nuclear signal. Genes Dev. 2005 Sep 1;19(17):1951-67. doi: 10.1101/gad.1331805. PMID:16140981 doi:http://dx.doi.org/10.1101/gad.1331805
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