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Article Dans Une Revue Journal of Physical Chemistry Letters Année : 2016

Repair Rate of Clustered Abasic DNA Lesions by Human Endonuclease: Molecular Bases of Sequence Specificity

Elise Dumont

Résumé

In the present contribution, the interaction between damaged DNA and repair enzymes is examined by means of molecular dynamics simulations. More specifically, we consider clustered abasic DNA lesions processed by the primary human apurinic/apyrimidinic (AP) endonuclease, APE1. Our results show that, in stark contrast with the corresponding bacterial endonucleases, human APE1 imposes strong geometrical constraints on the DNA duplex. As a consequence, the level of recognition and, hence, the repair rate is higher. Important features that guide the DNA/protein interactions are the presence of an extended positively charged region and of a molecular tweezers that strongly constrains DNA. Our results are on very good agreement with the experimentally determined repair rate of clustered abasic lesions. The lack of repair for one particular arrangement of the two abasic sites is also explained considering the peculiar destabilizing interaction between the recognition region and the second lesion, resulting in a partial opening of the molecular tweezers and, thus, a less stable complex. This contribution cogently establishes the molecular bases for the recognition and repair of clustered DNA lesions by means of human endonucleases.
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Dates et versions

hal-01449702 , version 1 (30-01-2017)

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Hugo Gattuso, Elodie Durand, Emmanuelle Bignon, Christophe Morell, Alexandros G. Georgakilas, et al.. Repair Rate of Clustered Abasic DNA Lesions by Human Endonuclease: Molecular Bases of Sequence Specificity. Journal of Physical Chemistry Letters, 2016, 7 (19), pp.3760-3765. ⟨10.1021/acs.jpclett.6b01692⟩. ⟨hal-01449702⟩
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