Photoselected electron transfer pathways in DNA photolyase

Area of Science:

• Biochemistry
• Photochemistry
• Molecular Biology

Background:

• Photolyases are proteins that repair UV-induced DNA damage.
• They utilize flavin adenine dinucleotide (FADH(-)) as an electron donor.
• Repair involves photo-induced electron transfer to cyclobutane pyrimidine dimers.

Purpose of the Study:

• To investigate the electronic structure of the photo-excited flavin adenine dinucleotide (FADH(-)) cofactor.
• To understand how FADH(-) facilitates electron transfer to DNA lesions.
• To elucidate the role of excited state localization in enhancing electron transfer rates.

Main Methods:

• Ab initio methods (TD-DFT, TD-HF) and semiempirical (INDO/S CI) calculations were used to compute FADH(-) excited states.
• Molecular dynamics simulations modeled protein-DNA interactions and cofactor conformations.
• Electronic coupling between FADH(-) and thymine dimers was calculated.

Main Results:

• The lowest excited singlet states of FADH(-) are localized on the flavin ring proximal to the DNA dimer.
• This localization creates shorter, more efficient electron transfer pathways.
• Electronic coupling is enhanced by the proximity and orientation of the excited FADH(-) state.

Conclusions:

• Photo-excitation of FADH(-) in photolyase leads to electron localization, enhancing electronic coupling.
• This mechanism facilitates rapid electron transfer from FADH(-) to the DNA lesion.
• The findings explain how photolyase efficiently repairs UV-damaged DNA.