Elahe Alizadeh

Bio: Elahe Alizadeh is an academic researcher from Université de Sherbrooke. The author has contributed to research in topics: Dissociation (chemistry) & DNA damage. The author has an hindex of 12, co-authored 19 publications receiving 777 citations. Previous affiliations of Elahe Alizadeh include University of Guelph.

Biomolecular Damage Induced by Ionizing Radiation: The Direct and Indirect Effects of Low-Energy Electrons on DNA

Abstract: Many experimental and theoretical advances have recently allowed the study of direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an effort to explain how LEEs damage the human genome, researchers have focused efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs, phosphate groups, and longer DNA moieties. Here, we summarize the current understanding of the fundamental mechanisms involved in LEE-induced damage of DNA and complex biomolecule films. Results obtained by several laboratories on films prepared and analyzed by different methods and irradiated with different electron-beam current densities and fluencies are presented. Despite varied conditions (e.g., film thicknesses and morphologies, intrinsic water content, substrate interactions, and extrinsic atmospheric compositions), comparisons show a striking resemblance in the types of damage produced and their yield functions. The potential of controlling this damage using molecular and nanoparticle targets with high LEE yields in targeted radiation-based cancer therapies is also discussed.

Precursors of solvated electrons in radiobiological physics and chemistry.

Abstract: s; Proceeding of IX ECSBM, Prague, Czech Republic, 2001. (176) Abouaf, R.; Pommier, J.; Dunet, H. Int. J. Mass Spectrom. 2003, 226, 397. (177) Denifl, S.; Ptasin ́ska, S.; Cingel, M.; Matejcik, S.; Scheier, P.; Mar̈k, T. D. Chem. Phys. Lett. 2003, 377, 74. (178) Gohlke, S.; Abdoul-Carime, H.; Illenberger, E. Chem. Phys. Lett. 2003, 380, 595. (179) Abdoul-Carime, H.; Gohlke, S.; Illenberger, E. Phys. Rev. Lett. 2004, 92, 168103. (180) Ptasin ́ska, S.; Denifl, S.; Grill, V.; Mar̈k, T. D.; Scheier, P.; Gohlke, S.; Huels, M. A.; Illenberger, E. Angew. Chem., Int. Ed. 2005, 44, 1657. (181) Aflatooni, K.; Gallup, G. A.; Burrow, P. D. J. Phys. Chem. A 1998, 102, 6205. (182) Burrow, P. D.; Gallup, G. A.; Scheer, A. M.; Denifl, S.; Ptasinska, S.; Mar̈k, T. D.; Scheier, P. J. Chem. Phys. 2006, 124, 124310. (183) Aflatooni, K.; Scheer, A. M.; Burrow, P. D. Chem. Phys. Lett. 2005, 408, 426. (184) Naaman, R.; Sanche, L. Chem. Rev. 2007, 107, 1553. (185) Li, X.; Sevilla, M. D.; Sanche, L. J. Phys. Chem. B 2004, 108, 19013. (186) Ptasin ́ska, S.; Denifl, S.; Mroź, B.; Probst, M.; Grill, V.; Illenberger, E.; Scheier, P.; Mar̈k, T. D. J. Chem. Phys. 2005, 123, 124302. (187) Li, Z.; Cloutier, P.; Sanche, L.; Wagner, J. R. J. Phys. Chem. B 2011, 115, 13668. (188) Li, X.; Sevilla, M. D.; Sanche, L. J. Phys. Chem. B 2004, 108, 5472. (189) Ptasin ́ska, S.; Denifl, S.; Scheier, P.; Illenberger, E.; Mar̈k, T. D. Angew. Chem., Int. Ed. 2005, 44, 6941. (190) Zheng, Y.; Cloutier, P.; Hunting, D. J.; Wagner, J. R.; Sanche, L. J. Am. Chem. Soc. 2004, 126, 1002. (191) Huels, M. A.; Parenteau, L.; Michaud, M.; Sanche, L. Phys. Rev. A 1995, 51, 337. (192) Abdoul-Carime, H.; Cloutier, P.; Sanche, L. Radiat. Res. 2001, 155, 625. (193) Baccarelli, I.; Bald, I.; Gianturco, F. A.; Illenberger, E.; Kopyra, J. Phys. Rep. 2011, 508, 1. (194) Ptasin ́ska, S.; Denifl, S.; Scheier, P.; Mar̈k, T. D. J. Chem. Phys. 2004, 120, 8505. (195) Antic, D.; Parenteau, L.; Lepage, M.; Sanche, L. J. Phys. Chem. 1999, 103, 6611. (196) Antic, D.; Parenteau, L.; Sanche, L. J. Phys. Chem. B 2000, 104, 4711. (197) Huels, M. A.; Parenteau, L.; Sanche, L. J. Phys. Chem. B 2004, 108, 16303. (198) Pan, X.; Sanche, L. Chem. Phys. Lett. 2006, 421, 404. (199) Pan, X.; Sanche, L. Phys. Rev. Lett. 2005, 94, 198104. (200) Sulzer, P.; Mauracher, A.; Denifl, S.; Zappa, F.; Ptasin ́ska, S.; Beikircher, M.; Bacher, A.; Wendt, N.; Aleem, A.; Rondino, F.; Matejcik, S.; Probst, M.; Mar̈k, T. D.; Scheier, P. Anal. Chem. 2007, 79, 6585. (201) Gu, J.; Xie, Y.; Schaefer, H. F. Chem.Eur. J. 2010, 16, 5089. (202) Zheng, Y.; Cloutier, P.; Hunting, D. J.; Sanche, L.; Wagner, J. R. J. Am. Chem. Soc. 2005, 127, 16592. (203) Zheng, Y.; Wagner, J. R.; Sanche, L. Phys. Rev. Lett. 2006, 96, 208101. (204) Zheng, Y.; Cloutier, P.; Hunting, D. J.; Wagner, J. R.; Sanche, L. J. Chem. Phys. 2006, 124, 9. (205) Huels, M.; Boudaïffa, B.; Cloutier, P.; Hunting, D. J.; Sanche, L. J. Am. Chem. Soc. 2003, 125, 4467. (206) Boudaïffa, B.; Hunting, D. J.; Cloutier, P.; Huels, M. A.; Sanche, L. Int. J. Radiat. Biol. 2000, 76, 1209. (207) Boudaïffa, B.; Cloutier, P.; Hunting, D. J.; Huels, M. A.; Sanche, L. Med. Sci 2000, 16, 1281. (208) Martin, F.; Burrow, P. D.; Cai, Z.; Cloutier, P.; Hunting, D. J.; Sanche, L. Phys. Rev. Lett. 2004, 93, 068101. (209) Panajotovic, R.; Martin, F.; Cloutier, P.; Hunting, D. J.; Sanche, L. Radiat. Res. 2006, 165, 452. (210) Li, X.; Sevilla, M. D.; Sanche, L. J. Am. Chem. Soc. 2003, 125, 13668. (211) Simons, J. Acc. Chem. Res. 2006, 39, 772. (212) Bao, X.; Wang, J.; Gu, J.; Leszczynski, J. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 5658. (213) Caron, L.; Sanche, L. Phys. Rev. A: At., Mol. Opt. Phys. 2004, 70, 032719. (214) Caron, L. G.; Sanche, L. In Low-energy Electron Scattering from Molecules, Biomolecules and Surfaces; Čaŕsky, P., Čurík, R., Eds.; CRC Press (Taylor and Francis Group): Boca Raton, FL, 2012; pp 161− 230. (215) Lin, S. D. Radiat. Res. 1974, 59, 521. (216) Abdoul-Carime, H.; Sanche, L. Radiat. Res. 2003, 160, 86. (217) Abdoul-Carime, H.; Sanche, L. J. Phys. Chem. B 2004, 108, 457. (218) Abdoul-Carime, H.; Cecchini, S.; Sanche, L. Radiat. Res. 2002, 158, 23. (219) Ptasin ́ska, S.; Denifl, S.; Candor, P.; Matejcik, S.; Scheier, P.; Mar̈k, T. D. Chem. Phys. Lett. 2005, 403, 107. (220) Abdoul-Carime, H.; Gohlke, S.; Illenberger, E. Chem. Phys. Lett. 2005, 402, 497. (221) Gohlke, S.; Rosa, A.; Illenberger, E.; Brüning, F.; Huels, M. A. J. Chem. Phys. 2002, 116, 10164. (222) Ptasin ́ska, S.; Denifl, S.; Abedi, A.; Scheier, P.; Mar̈k, T. D. Anal. Bioanal. Chem. 2003, 377, 1115. (223) Abdoul-Carime, H.; Illenberger, E. Chem. Phys. Lett. 2004, 397, 309. (224) Sulzer, P.; Alizadeh, E.; Mauracher, A.; Scheier, P.; Mar̈k, T. D. Int. J. Mass. Spectrom. 2008, 277, 274. (225) Abdoul-Carime, H.; Gohlke, S.; Illenberger, E. Phys. Chem. Chem. Phys. 2004, 6, 161. (226) Alizadeh, E. Dissociative Electron Attachment to Biomolecules. Ph.D Thesis, University of Innsbruck, Innsbruck, Austria, August 2009. (227) Alizadeh, E.; Gschliesser, D.; Bartl, P.; Edtbauer, A.; Vizcaino, V.; Mauracher, A.; Probst, M.; Mar̈k, T. D.; Ptasin ́ska, S.; Mason, N. J.; Denifl, S.; Scheier, P. J. Chem. Phys. 2011, 134, 054305. (228) Vasil’ev, Y. V.; Figard, B. J.; Barofsky, D. F.; Deinzer, M. L. J. Am. Chem. Soc. 2007, 268, 106. (229) Cloutier, P.; Sicard-Roselli, C.; Escher, E.; Sanche, L. J. Phys. Chem. B 2007, 111, 1620. (230) Ptasin ́ska, S.; Li, Z.; Mason, N. J.; Sanche, L. Phys. Chem. Chem. Phys. 2010, 12, 9367. (231) Wang, J.; Gu, J.; Leszczynski, J. Chem. Phys. Lett. 2007, 442, 124. (232) Ptasin ́ska, S.; Sanche, L. Phys. Rev. E 2007, 75, 031915. (233) Falk, M.; Hartman, K. A.; Lord, R. C. J. Am. Chem. Soc. 1963, 85, 387. (234) Orlando, T. M.; Oh, D.; Chen, Y.; Aleksandrov, A. B. J. Chem. Phys. 2008, 128, 195102. (235) Dumont, A.; Zheng, Y.; Hunting, D.; Sanche, L. J. Chem. Phys. 2010, 132, 045102. (236) Solomun, T.; Skalicky, T. Chem. Phys. Lett. 2008, 453, 101. (237) Lett, J. T.; Alexander, P. Radiat. Res. 1961, 15, 159. Chemical Reviews Review dx.doi.org/10.1021/cr300063r | Chem. Rev. XXXX, XXX, XXX−XXX X (238) Neary, G. J.; Simpson-Gildemeister, V. F. W.; Peacocke, A. R. Int. J. Radiat. Biol. 1970, 18, 25. (239) Hearst, J. E.; Vinogard, J. Proc. Natl. Acad. Sci. U.S.A. 1961, 47, 825. (240) Saenger, W. Principles of Nucleic Acid Structure; SpringerVerlag: New York, NY, 1984. (241) Jeffrey, G.; Saenger, W. Hydration Bonding in Biological Structures; Springer-Verlag: New York, NY, 1991. (242) Tao, N. J.; Lindsay, S. M.; Rupprecht, A. Biopolymers 1989, 28, 1019. (243) Swarts, S.; Sevilla, M. D.; Becker, D.; Tokar, C.; Wheeler, K. Radiat. Res. 1992, 129, 333. (244) Brun, É.; Cloutier, P.; Sicard-Roselli, C.; Fromm, M.; Sanche, L. J. Phys. Chem. B 2009, 113, 10008. (245) Cai, Z.; Cloutier, P.; Hunting, D. J.; Sanche, L. J. Phys. Chem. B 2005, 109, 4796. (246) de Lara, C. M.; Jenner, T. J.; Townsend, K. M. S.; Marsden, S. J.; O’Neill, P. Radiat. Res. 1995, 144, 43. (247) Alizadeh, E.; Cloutier, P.; Hunting, D. J.; Sanche, L. J. Phys. Chem. B 2011, 115, 4796. (248) Samuni, A.; Czapski, G. Radiat. Res. 1978, 76, 624. (249) Roots, R.; Chatterjee, A.; Blakely, E.; Chang, P.; Smith, K.; Tobias, C. Radiat. Res. 1982, 92, 245. (250) Ewing, D.; Walton, H. L.; Guilfoil, D. S.; Ohm, M. B. Int. J. Radiat. Biol. 1991, 59, 717. (251) Alizadeh, E.; Sanche, L. Radiat. Phys. Chem. 2012, 81, 33. (252) Nikjoo, H.; Lindborg, L. Phys. Med. Biol. 2010, 55, R65. (253) Alizadeh, E.; Sanche, L. J. Phys. Chem. B 2011, 115, 14852. (254) Devita Jr, V. T.; Hellman, S.; Resenberg, S. A. Cancer: Principles and Practice of Oncology; Lippincott Williams and Wilkins: New York, NY, 2001. (255) Saif, M. W.; Diaso, R. B. In Chemoradiation in Cancer Therapy; Choy, H., Ed.; Humana Press: Totowa, NJ, 2003; pp 23−44. (256) Jamieson, E. R.; Lippard, S. J. Chem. Rev. 1999, 99, 2467. (257) Lippard, S. J. Pure Appl. Chem. 1987, 59, 731. (258) Zheng, Y.; Hunting, D. J.; Ayotte, P.; Sanche, L. Phys. Rev. Lett. 2008, 100, 198101. (259) Rezaee, M.; Hunting, D. J.; Sanche, L. Results to be published. (260) Rezaee, M.; Alizadeh, E.; Hunting, D. J.; Sanche, L. Bioinorg. Chem. Appl. 2011, 2012, 1. (261) Seiwert, T. Y.; Salama, J. K.; Vokes, E. E. Nat. Clin. Pract. Oncol. 2007, 4, 86. (262) Zimbrick, J. D.; Sukrochana, A.; Richmond, R. C. Int. J. Radiat. Oncol. Biol. Phys. 1979, 5, 1351. (263) Lelieveld, P.; Scoles, M. A.; Brown, J. M.; Kallman, R. F. Int. J. Radiat. Oncol. Biol. Phys. 1985, 11, 111. (264) Sanche, L. Chem. Phys. Lett. 2009, 474, 1 (and references therein). (265) Zheng, Y.; Hunting, D. J.; Ayotte, P.; Sanche, L. Radiat. Res. 2008, 169, 19. (266) Heb́ert, E. M.; debouttier̀e, P. J.; Lepage, M.; Sanche, L.; Hunting, D. J. Int. J. Radiat. Biol. 2010, 86, 692. (267) Herold, D. M.; Das, I. J.; Stobbe, C. C.; Iyer, R. V.; Chapman, J. D. Int. J. Radiat. Biol. 2000, 76, 1357. (268) Whyman, R. Gold Bull. 1996, 29, 11. (269) Chen, W.; Zhang, J. J. Nanosci. Nanotechnol. 2006, 6, 1159. (270) Anshup, A.; Venkataraman, J. S.; Subramaniam, C.; Kumar, R. R.; Priya, S.; Kumar, T. R. S.; Omkumar, R. V.; John, A.; Pradeep, T. Langmuir 2005, 21, 11562. (271) Niidome, T.; Nakashima, K.; Takahashi, H.; Niidome, Y. Chem. Commun. 2004, 17, 1978. (272) Brun, E.; Duchambon, P.; Blouquit, Y.; Keller, G.; Sanche, L.; Sicard-Roselli, C. Radiat. Phys. Chem. 2009, 78, 177. (273) Foley, E. A.; Carter, J. D.; Shan, F.; Guo, T. Chem. Commun. 2005, 25, 3192. (274) Carter, J. D.; Cheng, N. N.; Qu, Y.; Suarez, G. D.; Guo, T. J. Phys. Chem. B 2007, 111, 11622. (275) Butterworth, K. T.; Wyer, J. A.; Brennan-Fournet, M.; Latimer, C. J.; Shah, M. B.; Currell, F. J.; Hirst, D. G. Radiat. Res. 2008, 170, 381. (276) Chang, M.; Shiau, A.; Chen, Y.; Chang, C.; Chen, H.; Wu, C. Cancer Sci. 2008, 99, 1479. (277) Xiao, F.; Zheng, Z.; Cloutier, P.; He, Y.; Hunting, D. J.; Sanche, L. Nanotechnology 2011, 22, 465101. (278) Zheng, Y.; Sanche, L. Radiat. Res. 2009, 172, 114. (279) German, E. D.;

Radiation Damage to DNA: The Indirect Effect of Low Energy Electrons.

Abstract: We report the effect of the DNA hydration level on damage yields induced by soft X-rays and photoemitted low-energy electrons (LEEs) in thin films of plasmid DNA irradiated in N2 at atmospheric pressure under different humidity levels. Contrary to a dilute solution of DNA, the number of H2O molecules per nucleotide (Γ) in these films can be varied from Γ = 2.5 to ∼33, where Γ ≤ 20 corresponds to layers of hydration and Γ = 33 to an additional bulk-like water layer. Our results indicate that DNA damage induced by LEEs does not increase significantly until the second hydration shell is formed. However, this damage increases dramatically as DNA coverage approaches bulk-like hydration conditions. A number of phenomena are invoked to account for these behaviors, including dissociative electron transfer from water–interface electron traps to DNA bases, quenching of dissociative electron attachment to DNA, and quenching of dissociative electronically excited states of H2O in contact with DNA.

A Single Subexcitation‐Energy Electron Can Induce a Double‐Strand Break in DNA Modified by Platinum Chemotherapeutic Drugs

Abstract: The sensitization of malignant cells to ionizing radiation is the clinical rationale for the use of platinum-drug-based concurrent chemoradiotherapy (CCRT) for cancer treatment; however, the specific mechanisms of radiosensitization and their respective contributions still remain unknown Biological mechanisms such as inhibition of DNA repair may contribute to the efficacy of CCRT; nevertheless, there is a dearth of information on the possible contribution of nanoscopic mechanisms to the generation of lethal DNA lesions, such as double-strand breaks (DSB) The present study demonstrates that the abundant near zero-eV (05 eV) electrons, created by ionizing radiation during radiotherapy, induce DSB in supercoiled plasmid DNA modified by platinum-containing anticancer drugs (Pt drugs), but not in unmodified DNA They do so more efficiently than other types of radiation, including soft X-rays and 10 eV electrons The formation of DSB by 05 eV electrons is found to be a single-hit process These findings reveal insights into the radiosensitization mechanism of Pt drugs that can have implications for the development of optimal clinical protocols for platinum-based CCRT and the deployment of in situ sources of subexcitation-energy electrons (eg, Auger electron-emitting radionuclides) to efficiently enhance DSB formation in DNA modified by Pt drugs in malignant cells

Soft X-ray and low energy electron-induced damage to DNA under N2 and O2 atmospheres.

Abstract: DNA damage induced by low energy electrons (LEEs) and soft X-rays is measured under dry nitrogen and oxygen at atmospheric pressure and temperature. Five-monolayer plasmid DNA films deposited on tantalum and glass substrates are exposed to Al K(α) X-rays of 1.5 keV in the two different environments. From the damage yields for DNA, G values are extracted for X-rays and LEEs. The G values for LEEs are 3.5 and 3.4 higher than those for X-ray photons under N(2) and O(2) atmospheres, respectively. Because most of the measured damage is in the form of single strand breaks (SSB), this result indicates a much higher effectiveness for LEEs relative to X-rays in causing SSB in both environments. The results indicate that the oxygen fixation mechanism, which is highly effective in increasing radiobiological effectiveness, under aerobic conditions, is operative on the type of damage created at the early stage of DNA radiolysis by LEEs.

Plasma-liquid interactions: A review and roadmap

Abstract: Plasma–liquid interactions represent a growing interdisciplinary area of research involving plasma science, fluid dynamics, heat and mass transfer, photolysis, multiphase chemistry and aerosol science. This review provides an assessment of the state-of-the-art of this multidisciplinary area and identifies the key research challenges. The developments in diagnostics, modeling and further extensions of cross section and reaction rate databases that are necessary to address these challenges are discussed. The review focusses on non-equilibrium plasmas.

Software for the frontiers of quantum chemistry: An overview of developments in the Q-Chem 5 package

Abstract: This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange-correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear-electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an "open teamware" model and an increasingly modular design.

Biomolecular Damage Induced by Ionizing Radiation: The Direct and Indirect Effects of Low-Energy Electrons on DNA

Abstract: Many experimental and theoretical advances have recently allowed the study of direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an effort to explain how LEEs damage the human genome, researchers have focused efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs, phosphate groups, and longer DNA moieties. Here, we summarize the current understanding of the fundamental mechanisms involved in LEE-induced damage of DNA and complex biomolecule films. Results obtained by several laboratories on films prepared and analyzed by different methods and irradiated with different electron-beam current densities and fluencies are presented. Despite varied conditions (e.g., film thicknesses and morphologies, intrinsic water content, substrate interactions, and extrinsic atmospheric compositions), comparisons show a striking resemblance in the types of damage produced and their yield functions. The potential of controlling this damage using molecular and nanoparticle targets with high LEE yields in targeted radiation-based cancer therapies is also discussed.

Precursors of solvated electrons in radiobiological physics and chemistry.

Abstract: s; Proceeding of IX ECSBM, Prague, Czech Republic, 2001. (176) Abouaf, R.; Pommier, J.; Dunet, H. Int. J. Mass Spectrom. 2003, 226, 397. (177) Denifl, S.; Ptasin ́ska, S.; Cingel, M.; Matejcik, S.; Scheier, P.; Mar̈k, T. D. Chem. Phys. Lett. 2003, 377, 74. (178) Gohlke, S.; Abdoul-Carime, H.; Illenberger, E. Chem. Phys. Lett. 2003, 380, 595. (179) Abdoul-Carime, H.; Gohlke, S.; Illenberger, E. Phys. Rev. Lett. 2004, 92, 168103. (180) Ptasin ́ska, S.; Denifl, S.; Grill, V.; Mar̈k, T. D.; Scheier, P.; Gohlke, S.; Huels, M. A.; Illenberger, E. Angew. Chem., Int. Ed. 2005, 44, 1657. (181) Aflatooni, K.; Gallup, G. A.; Burrow, P. D. J. Phys. Chem. A 1998, 102, 6205. (182) Burrow, P. D.; Gallup, G. A.; Scheer, A. M.; Denifl, S.; Ptasinska, S.; Mar̈k, T. D.; Scheier, P. J. Chem. Phys. 2006, 124, 124310. (183) Aflatooni, K.; Scheer, A. M.; Burrow, P. D. Chem. Phys. Lett. 2005, 408, 426. (184) Naaman, R.; Sanche, L. Chem. Rev. 2007, 107, 1553. (185) Li, X.; Sevilla, M. D.; Sanche, L. J. Phys. Chem. B 2004, 108, 19013. (186) Ptasin ́ska, S.; Denifl, S.; Mroź, B.; Probst, M.; Grill, V.; Illenberger, E.; Scheier, P.; Mar̈k, T. D. J. Chem. Phys. 2005, 123, 124302. (187) Li, Z.; Cloutier, P.; Sanche, L.; Wagner, J. R. J. Phys. Chem. B 2011, 115, 13668. (188) Li, X.; Sevilla, M. D.; Sanche, L. J. Phys. Chem. B 2004, 108, 5472. (189) Ptasin ́ska, S.; Denifl, S.; Scheier, P.; Illenberger, E.; Mar̈k, T. D. Angew. Chem., Int. Ed. 2005, 44, 6941. (190) Zheng, Y.; Cloutier, P.; Hunting, D. J.; Wagner, J. R.; Sanche, L. J. Am. Chem. Soc. 2004, 126, 1002. (191) Huels, M. A.; Parenteau, L.; Michaud, M.; Sanche, L. Phys. Rev. A 1995, 51, 337. (192) Abdoul-Carime, H.; Cloutier, P.; Sanche, L. Radiat. Res. 2001, 155, 625. (193) Baccarelli, I.; Bald, I.; Gianturco, F. A.; Illenberger, E.; Kopyra, J. Phys. Rep. 2011, 508, 1. (194) Ptasin ́ska, S.; Denifl, S.; Scheier, P.; Mar̈k, T. D. J. Chem. Phys. 2004, 120, 8505. (195) Antic, D.; Parenteau, L.; Lepage, M.; Sanche, L. J. Phys. Chem. 1999, 103, 6611. (196) Antic, D.; Parenteau, L.; Sanche, L. J. Phys. Chem. B 2000, 104, 4711. (197) Huels, M. A.; Parenteau, L.; Sanche, L. J. Phys. Chem. B 2004, 108, 16303. (198) Pan, X.; Sanche, L. Chem. Phys. Lett. 2006, 421, 404. (199) Pan, X.; Sanche, L. Phys. Rev. Lett. 2005, 94, 198104. (200) Sulzer, P.; Mauracher, A.; Denifl, S.; Zappa, F.; Ptasin ́ska, S.; Beikircher, M.; Bacher, A.; Wendt, N.; Aleem, A.; Rondino, F.; Matejcik, S.; Probst, M.; Mar̈k, T. D.; Scheier, P. Anal. Chem. 2007, 79, 6585. (201) Gu, J.; Xie, Y.; Schaefer, H. F. Chem.Eur. J. 2010, 16, 5089. (202) Zheng, Y.; Cloutier, P.; Hunting, D. J.; Sanche, L.; Wagner, J. R. J. Am. Chem. Soc. 2005, 127, 16592. (203) Zheng, Y.; Wagner, J. R.; Sanche, L. Phys. Rev. Lett. 2006, 96, 208101. (204) Zheng, Y.; Cloutier, P.; Hunting, D. J.; Wagner, J. R.; Sanche, L. J. Chem. Phys. 2006, 124, 9. (205) Huels, M.; Boudaïffa, B.; Cloutier, P.; Hunting, D. J.; Sanche, L. J. Am. Chem. Soc. 2003, 125, 4467. (206) Boudaïffa, B.; Hunting, D. J.; Cloutier, P.; Huels, M. A.; Sanche, L. Int. J. Radiat. Biol. 2000, 76, 1209. (207) Boudaïffa, B.; Cloutier, P.; Hunting, D. J.; Huels, M. A.; Sanche, L. Med. Sci 2000, 16, 1281. (208) Martin, F.; Burrow, P. D.; Cai, Z.; Cloutier, P.; Hunting, D. J.; Sanche, L. Phys. Rev. Lett. 2004, 93, 068101. (209) Panajotovic, R.; Martin, F.; Cloutier, P.; Hunting, D. J.; Sanche, L. Radiat. Res. 2006, 165, 452. (210) Li, X.; Sevilla, M. D.; Sanche, L. J. Am. Chem. Soc. 2003, 125, 13668. (211) Simons, J. Acc. Chem. Res. 2006, 39, 772. (212) Bao, X.; Wang, J.; Gu, J.; Leszczynski, J. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 5658. (213) Caron, L.; Sanche, L. Phys. Rev. A: At., Mol. Opt. Phys. 2004, 70, 032719. (214) Caron, L. G.; Sanche, L. In Low-energy Electron Scattering from Molecules, Biomolecules and Surfaces; Čaŕsky, P., Čurík, R., Eds.; CRC Press (Taylor and Francis Group): Boca Raton, FL, 2012; pp 161− 230. (215) Lin, S. D. Radiat. Res. 1974, 59, 521. (216) Abdoul-Carime, H.; Sanche, L. Radiat. Res. 2003, 160, 86. (217) Abdoul-Carime, H.; Sanche, L. J. Phys. Chem. B 2004, 108, 457. (218) Abdoul-Carime, H.; Cecchini, S.; Sanche, L. Radiat. Res. 2002, 158, 23. (219) Ptasin ́ska, S.; Denifl, S.; Candor, P.; Matejcik, S.; Scheier, P.; Mar̈k, T. D. Chem. Phys. Lett. 2005, 403, 107. (220) Abdoul-Carime, H.; Gohlke, S.; Illenberger, E. Chem. Phys. Lett. 2005, 402, 497. (221) Gohlke, S.; Rosa, A.; Illenberger, E.; Brüning, F.; Huels, M. A. J. Chem. Phys. 2002, 116, 10164. (222) Ptasin ́ska, S.; Denifl, S.; Abedi, A.; Scheier, P.; Mar̈k, T. D. Anal. Bioanal. Chem. 2003, 377, 1115. (223) Abdoul-Carime, H.; Illenberger, E. Chem. Phys. Lett. 2004, 397, 309. (224) Sulzer, P.; Alizadeh, E.; Mauracher, A.; Scheier, P.; Mar̈k, T. D. Int. J. Mass. Spectrom. 2008, 277, 274. (225) Abdoul-Carime, H.; Gohlke, S.; Illenberger, E. Phys. Chem. Chem. Phys. 2004, 6, 161. (226) Alizadeh, E. Dissociative Electron Attachment to Biomolecules. Ph.D Thesis, University of Innsbruck, Innsbruck, Austria, August 2009. (227) Alizadeh, E.; Gschliesser, D.; Bartl, P.; Edtbauer, A.; Vizcaino, V.; Mauracher, A.; Probst, M.; Mar̈k, T. D.; Ptasin ́ska, S.; Mason, N. J.; Denifl, S.; Scheier, P. J. Chem. Phys. 2011, 134, 054305. (228) Vasil’ev, Y. V.; Figard, B. J.; Barofsky, D. F.; Deinzer, M. L. J. Am. Chem. Soc. 2007, 268, 106. (229) Cloutier, P.; Sicard-Roselli, C.; Escher, E.; Sanche, L. J. Phys. Chem. B 2007, 111, 1620. (230) Ptasin ́ska, S.; Li, Z.; Mason, N. J.; Sanche, L. Phys. Chem. Chem. Phys. 2010, 12, 9367. (231) Wang, J.; Gu, J.; Leszczynski, J. Chem. Phys. Lett. 2007, 442, 124. (232) Ptasin ́ska, S.; Sanche, L. Phys. Rev. E 2007, 75, 031915. (233) Falk, M.; Hartman, K. A.; Lord, R. C. J. Am. Chem. Soc. 1963, 85, 387. (234) Orlando, T. M.; Oh, D.; Chen, Y.; Aleksandrov, A. B. J. Chem. Phys. 2008, 128, 195102. (235) Dumont, A.; Zheng, Y.; Hunting, D.; Sanche, L. J. Chem. Phys. 2010, 132, 045102. (236) Solomun, T.; Skalicky, T. Chem. Phys. Lett. 2008, 453, 101. (237) Lett, J. T.; Alexander, P. Radiat. Res. 1961, 15, 159. Chemical Reviews Review dx.doi.org/10.1021/cr300063r | Chem. Rev. XXXX, XXX, XXX−XXX X (238) Neary, G. J.; Simpson-Gildemeister, V. F. W.; Peacocke, A. R. Int. J. Radiat. Biol. 1970, 18, 25. (239) Hearst, J. E.; Vinogard, J. Proc. Natl. Acad. Sci. U.S.A. 1961, 47, 825. (240) Saenger, W. Principles of Nucleic Acid Structure; SpringerVerlag: New York, NY, 1984. (241) Jeffrey, G.; Saenger, W. Hydration Bonding in Biological Structures; Springer-Verlag: New York, NY, 1991. (242) Tao, N. J.; Lindsay, S. M.; Rupprecht, A. Biopolymers 1989, 28, 1019. (243) Swarts, S.; Sevilla, M. D.; Becker, D.; Tokar, C.; Wheeler, K. Radiat. Res. 1992, 129, 333. (244) Brun, É.; Cloutier, P.; Sicard-Roselli, C.; Fromm, M.; Sanche, L. J. Phys. Chem. B 2009, 113, 10008. (245) Cai, Z.; Cloutier, P.; Hunting, D. J.; Sanche, L. J. Phys. Chem. B 2005, 109, 4796. (246) de Lara, C. M.; Jenner, T. J.; Townsend, K. M. S.; Marsden, S. J.; O’Neill, P. Radiat. Res. 1995, 144, 43. (247) Alizadeh, E.; Cloutier, P.; Hunting, D. J.; Sanche, L. J. Phys. Chem. B 2011, 115, 4796. (248) Samuni, A.; Czapski, G. Radiat. Res. 1978, 76, 624. (249) Roots, R.; Chatterjee, A.; Blakely, E.; Chang, P.; Smith, K.; Tobias, C. Radiat. Res. 1982, 92, 245. (250) Ewing, D.; Walton, H. L.; Guilfoil, D. S.; Ohm, M. B. Int. J. Radiat. Biol. 1991, 59, 717. (251) Alizadeh, E.; Sanche, L. Radiat. Phys. Chem. 2012, 81, 33. (252) Nikjoo, H.; Lindborg, L. Phys. Med. Biol. 2010, 55, R65. (253) Alizadeh, E.; Sanche, L. J. Phys. Chem. B 2011, 115, 14852. (254) Devita Jr, V. T.; Hellman, S.; Resenberg, S. A. Cancer: Principles and Practice of Oncology; Lippincott Williams and Wilkins: New York, NY, 2001. (255) Saif, M. W.; Diaso, R. B. In Chemoradiation in Cancer Therapy; Choy, H., Ed.; Humana Press: Totowa, NJ, 2003; pp 23−44. (256) Jamieson, E. R.; Lippard, S. J. Chem. Rev. 1999, 99, 2467. (257) Lippard, S. J. Pure Appl. Chem. 1987, 59, 731. (258) Zheng, Y.; Hunting, D. J.; Ayotte, P.; Sanche, L. Phys. Rev. Lett. 2008, 100, 198101. (259) Rezaee, M.; Hunting, D. J.; Sanche, L. Results to be published. (260) Rezaee, M.; Alizadeh, E.; Hunting, D. J.; Sanche, L. Bioinorg. Chem. Appl. 2011, 2012, 1. (261) Seiwert, T. Y.; Salama, J. K.; Vokes, E. E. Nat. Clin. Pract. Oncol. 2007, 4, 86. (262) Zimbrick, J. D.; Sukrochana, A.; Richmond, R. C. Int. J. Radiat. Oncol. Biol. Phys. 1979, 5, 1351. (263) Lelieveld, P.; Scoles, M. A.; Brown, J. M.; Kallman, R. F. Int. J. Radiat. Oncol. Biol. Phys. 1985, 11, 111. (264) Sanche, L. Chem. Phys. Lett. 2009, 474, 1 (and references therein). (265) Zheng, Y.; Hunting, D. J.; Ayotte, P.; Sanche, L. Radiat. Res. 2008, 169, 19. (266) Heb́ert, E. M.; debouttier̀e, P. J.; Lepage, M.; Sanche, L.; Hunting, D. J. Int. J. Radiat. Biol. 2010, 86, 692. (267) Herold, D. M.; Das, I. J.; Stobbe, C. C.; Iyer, R. V.; Chapman, J. D. Int. J. Radiat. Biol. 2000, 76, 1357. (268) Whyman, R. Gold Bull. 1996, 29, 11. (269) Chen, W.; Zhang, J. J. Nanosci. Nanotechnol. 2006, 6, 1159. (270) Anshup, A.; Venkataraman, J. S.; Subramaniam, C.; Kumar, R. R.; Priya, S.; Kumar, T. R. S.; Omkumar, R. V.; John, A.; Pradeep, T. Langmuir 2005, 21, 11562. (271) Niidome, T.; Nakashima, K.; Takahashi, H.; Niidome, Y. Chem. Commun. 2004, 17, 1978. (272) Brun, E.; Duchambon, P.; Blouquit, Y.; Keller, G.; Sanche, L.; Sicard-Roselli, C. Radiat. Phys. Chem. 2009, 78, 177. (273) Foley, E. A.; Carter, J. D.; Shan, F.; Guo, T. Chem. Commun. 2005, 25, 3192. (274) Carter, J. D.; Cheng, N. N.; Qu, Y.; Suarez, G. D.; Guo, T. J. Phys. Chem. B 2007, 111, 11622. (275) Butterworth, K. T.; Wyer, J. A.; Brennan-Fournet, M.; Latimer, C. J.; Shah, M. B.; Currell, F. J.; Hirst, D. G. Radiat. Res. 2008, 170, 381. (276) Chang, M.; Shiau, A.; Chen, Y.; Chang, C.; Chen, H.; Wu, C. Cancer Sci. 2008, 99, 1479. (277) Xiao, F.; Zheng, Z.; Cloutier, P.; He, Y.; Hunting, D. J.; Sanche, L. Nanotechnology 2011, 22, 465101. (278) Zheng, Y.; Sanche, L. Radiat. Res. 2009, 172, 114. (279) German, E. D.;

The Unfolded Protein Response: Detecting and Responding to Fluctuations in the Protein-Folding Capacity of the Endoplasmic Reticulum

Abstract: Most of the secreted and plasma membrane proteins are synthesized on membrane-bound ribosomes on the endoplasmic reticulum (ER). They require engagement of ER-resident chaperones and foldases that assist in their folding and maturation. Since protein homeostasis in the ER is crucial for cellular function, the protein-folding status in the organelle's lumen is continually surveyed by a network of signaling pathways, collectively called the unfolded protein response (UPR). Protein-folding imbalances, or "ER stress," are detected by highly conserved sensors that adjust the ER's protein-folding capacity according to the physiological needs of the cell. We review recent developments in the field that have provided new insights into the ER stress-sensing mechanisms used by UPR sensors and the mechanisms by which they integrate various cellular inputs to adjust the folding capacity of the organelle to accommodate to fluctuations in ER protein-folding demands.