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| 001 | 276790 | ||
| 005 | 20240918112836.0 | ||
| 024 | 7 | _ | |a 10.1073/pnas.2220132120 |2 doi |
| 024 | 7 | _ | |a pmid:37307476 |2 pmid |
| 024 | 7 | _ | |a 0027-8424 |2 ISSN |
| 024 | 7 | _ | |a 1091-6490 |2 ISSN |
| 024 | 7 | _ | |a altmetric:150260039 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2023-01165 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Schmalz, Michael |b 0 |
| 245 | _ | _ | |a Dissection of DNA damage and repair pathways in live cells by femtosecond laser microirradiation and free-electron modeling. |
| 260 | _ | _ | |a Washington, DC |c 2023 |b National Acad. of Sciences |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #LA:W650# |
| 520 | _ | _ | |a Understanding and predicting the outcome of the interaction of light with DNA has a significant impact on the study of DNA repair and radiotherapy. We report on a combination of femtosecond pulsed laser microirradiation at different wavelengths, quantitative imaging, and numerical modeling that yields a comprehensive picture of photon-mediated and free-electron-mediated DNA damage pathways in live cells. Laser irradiation was performed under highly standardized conditions at four wavelengths between 515 nm and 1,030 nm, enabling to study two-photon photochemical and free-electron-mediated DNA damage in situ. We quantitatively assessed cyclobutane pyrimidine dimer (CPD) and γH2AX-specific immunofluorescence signals to calibrate the damage threshold dose at these wavelengths and performed a comparative analysis of the recruitment of DNA repair factors xeroderma pigmentosum complementation group C (XPC) and Nijmegen breakage syndrome 1 (Nbs1). Our results show that two-photon-induced photochemical CPD generation dominates at 515 nm, while electron-mediated damage dominates at wavelengths ≥620 nm. The recruitment analysis revealed a cross talk between nucleotide excision and homologous recombination DNA repair pathways at 515 nm. Numerical simulations predicted electron densities and electron energy spectra, which govern the yield functions of a variety of direct electron-mediated DNA damage pathways and of indirect damage by •OH radicals resulting from laser and electron interactions with water. Combining these data with information on free electron-DNA interactions gained in artificial systems, we provide a conceptual framework for the interpretation of the wavelength dependence of laser-induced DNA damage that may guide the selection of irradiation parameters in studies and applications that require the selective induction of DNA lesions. |
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| 650 | _ | 7 | |a DNA strand breaks |2 Other |
| 650 | _ | 7 | |a nonlinear photodamage |2 Other |
| 650 | _ | 7 | |a oxidative DNA damage |2 Other |
| 650 | _ | 7 | |a reductive DNA damage |2 Other |
| 650 | _ | 7 | |a wavelength selectivity |2 Other |
| 700 | 1 | _ | |a Liang, Xiao-Xuan |0 0000-0002-8325-1627 |b 1 |
| 700 | 1 | _ | |a Wieser, Ines |b 2 |
| 700 | 1 | _ | |a Gruschel, Caroline |0 0009-0000-7452-5326 |b 3 |
| 700 | 1 | _ | |a Muskalla, Lukas |b 4 |
| 700 | 1 | _ | |a Stöckl, Martin Thomas |b 5 |
| 700 | 1 | _ | |a Nitschke, Roland |0 0000-0002-9397-8475 |b 6 |
| 700 | 1 | _ | |a Linz, Norbert |0 0000-0002-7843-5966 |b 7 |
| 700 | 1 | _ | |a Leitenstorfer, Alfred |0 0000-0002-9847-257X |b 8 |
| 700 | 1 | _ | |a Vogel, Alfred |0 0000-0002-4371-9037 |b 9 |
| 700 | 1 | _ | |a Ferrando-May, Elisa |0 0000-0002-5567-8690 |b 10 |e Last author |
| 773 | _ | _ | |a 10.1073/pnas.2220132120 |g Vol. 120, no. 25, p. e2220132120 |0 PERI:(DE-600)1461794-8 |n 25 |p e2220132120 |t Proceedings of the National Academy of Sciences of the United States of America |v 120 |y 2023 |x 0027-8424 |
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| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 10 |6 0000-0002-5567-8690 |
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