SIRT1/PARP1 Crosstalk: Connecting DNA Damage and Metabolism

Overview

Journal Genome Integr

Date 2013 Dec 24

PMID 24360018

Citations 51

Authors

Augustin Luna

Mirit I Aladjem

Kurt W Kohn

Affiliations

Soon will be listed here.

Abstract

An intricate network regulates the activities of SIRT1 and PARP1 proteins and continues to be uncovered. Both SIRT1 and PARP1 share a common co-factor nicotinamide adenine dinucleotide (NAD+) and several common substrates, including regulators of DNA damage response and circadian rhythms. We review this complex network using an interactive Molecular Interaction Map (MIM) to explore the interplay between these two proteins. Here we discuss how NAD + competition and post-transcriptional/translational feedback mechanisms create a regulatory network sensitive to environmental cues, such as genotoxic stress and metabolic states, and examine the role of those interactions in DNA repair and ultimately, cell fate decisions.

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References

Vakhrusheva O, Smolka C, Gajawada P, Kostin S, Boettger T, Kubin T . Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ Res. 2008; 102(6):703-10. DOI: 10.1161/CIRCRESAHA.107.164558. View

Luna A, Sunshine M, van Iersel M, Aladjem M, Kohn K . PathVisio-MIM: PathVisio plugin for creating and editing Molecular Interaction Maps (MIMs). Bioinformatics. 2011; 27(15):2165-6. PMC: 3137219. DOI: 10.1093/bioinformatics/btr336. View

Yuan J, Minter-Dykhouse K, Lou Z . A c-Myc-SIRT1 feedback loop regulates cell growth and transformation. J Cell Biol. 2009; 185(2):203-11. PMC: 2700370. DOI: 10.1083/jcb.200809167. View

Guo X, Williams J, Schug T, Li X . DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. J Biol Chem. 2010; 285(17):13223-32. PMC: 2857074. DOI: 10.1074/jbc.M110.102574. View

Saunders L, Verdin E . Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene. 2007; 26(37):5489-504. DOI: 10.1038/sj.onc.1210616. View

DAmours D, Desnoyers S, DSilva I, Poirier G . Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999; 342 ( Pt 2):249-68. PMC: 1220459. View

Rouleau M, Patel A, Hendzel M, Kaufmann S, Poirier G . PARP inhibition: PARP1 and beyond. Nat Rev Cancer. 2010; 10(4):293-301. PMC: 2910902. DOI: 10.1038/nrc2812. View

Yuan Z, Seto E . A functional link between SIRT1 deacetylase and NBS1 in DNA damage response. Cell Cycle. 2007; 6(23):2869-71. DOI: 10.4161/cc.6.23.5026. View

Iijima K, Muranaka C, Kobayashi J, Sakamoto S, Komatsu K, Matsuura S . NBS1 regulates a novel apoptotic pathway through Bax activation. DNA Repair (Amst). 2008; 7(10):1705-16. DOI: 10.1016/j.dnarep.2008.06.013. View

10.

Villalba J, de Cabo R, Alcain F . A patent review of sirtuin activators: an update. Expert Opin Ther Pat. 2012; 22(4):355-67. DOI: 10.1517/13543776.2012.669374. View

11.

Kang H, Suh J, Jung Y, Jung J, Kim M, Chung J . Peptide switch is essential for Sirt1 deacetylase activity. Mol Cell. 2011; 44(2):203-13. PMC: 3240942. DOI: 10.1016/j.molcel.2011.07.038. View

12.

Liszt G, Ford E, Kurtev M, Guarente L . Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J Biol Chem. 2005; 280(22):21313-20. DOI: 10.1074/jbc.M413296200. View

13.

Salazar C, Brummer A, Alberghina L, Hofer T . Timing control in regulatory networks by multisite protein modifications. Trends Cell Biol. 2010; 20(11):634-41. DOI: 10.1016/j.tcb.2010.08.012. View

14.

Kanai M, Hanashiro K, Kim S, Hanai S, Boulares A, Miwa M . Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Nat Cell Biol. 2007; 9(10):1175-83. DOI: 10.1038/ncb1638. View

15.

Kim J, Chen J, Lou Z . DBC1 is a negative regulator of SIRT1. Nature. 2008; 451(7178):583-6. DOI: 10.1038/nature06500. View

16.

Wang C, Chen L, Hou X, Li Z, Kabra N, Ma Y . Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 2006; 8(9):1025-31. DOI: 10.1038/ncb1468. View

17.

Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F . SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008; 134(2):317-28. DOI: 10.1016/j.cell.2008.06.050. View

18.

Messner S, Altmeyer M, Zhao H, Pozivil A, Roschitzki B, Gehrig P . PARP1 ADP-ribosylates lysine residues of the core histone tails. Nucleic Acids Res. 2010; 38(19):6350-62. PMC: 2965223. DOI: 10.1093/nar/gkq463. View

19.

Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D . The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008; 134(2):329-40. PMC: 3526943. DOI: 10.1016/j.cell.2008.07.002. View

20.

Kim S, Lu H, Alano C . Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron culture. PLoS One. 2011; 6(3):e14731. PMC: 3046953. DOI: 10.1371/journal.pone.0014731. View