Quantum Chemical Study of the Enzymatic Repair of T(6-4)C/C(6-4)T UV-Photolesions by DNA Photolyases

Authors

  • Dr. Shirin Faraji,

    Corresponding author
    1. Interdisciplinary Center for Scientific Computing, Ruprecht-Karls University, Im Neuenheimer Feld 368, 69120 Heidelberg (Germany), Fax: (+49) (0)6221 548868
    • Interdisciplinary Center for Scientific Computing, Ruprecht-Karls University, Im Neuenheimer Feld 368, 69120 Heidelberg (Germany), Fax: (+49) (0)6221 548868
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  • Lukas Wirz,

    1. Interdisciplinary Center for Scientific Computing, Ruprecht-Karls University, Im Neuenheimer Feld 368, 69120 Heidelberg (Germany), Fax: (+49) (0)6221 548868
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  • Prof. Dr. Andreas Dreuw

    Corresponding author
    1. Interdisciplinary Center for Scientific Computing, Ruprecht-Karls University, Im Neuenheimer Feld 368, 69120 Heidelberg (Germany), Fax: (+49) (0)6221 548868
    • Interdisciplinary Center for Scientific Computing, Ruprecht-Karls University, Im Neuenheimer Feld 368, 69120 Heidelberg (Germany), Fax: (+49) (0)6221 548868
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Abstract

Several strategies have evolved to repair one of the abundant UV radiation-induced damages caused to DNA, namely the mutagenic pyrimidine (6-4) pyrimidone photolesions. DNA (6-4)-photolyases are enzymes repairing these lesions by a photoinitiated electron transfer. An important aspect of a possible repair mechanism is its generality and transferability to different (6-4) lesions. Therefore, previously suggested mechanisms for the repair of the T(6-4)T lesion are here transferred to the T(6-4)C and C(6-4)T lesions and investigated theoretically using quantum chemical methods. Despite the different functional groups of the pyrimidine bases involved, a general valid molecular mechanism was identified, in which the initial step is an electron transfer coupled to a proton transfer from the protonated HIS365 to the N3 nitrogen of the 3 pyrimidine, followed by an intramolecular OH/NH2 transfer in one concerted step, which does not require an oxetane/azetidine or isolated water/ammonia intermediate.

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