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@ARTICLE{Schmalz:276790,
      author       = {M. Schmalz and X.-X. Liang and I. Wieser and C. Gruschel
                      and L. Muskalla and M. T. Stöckl and R. Nitschke and N.
                      Linz and A. Leitenstorfer and A. Vogel and E.
                      Ferrando-May$^*$},
      title        = {{D}issection of {DNA} damage and repair pathways in live
                      cells by femtosecond laser microirradiation and
                      free-electron modeling.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {120},
      number       = {25},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DKFZ-2023-01165},
      pages        = {e2220132120},
      year         = {2023},
      note         = {#LA:W650#},
      abstract     = {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.},
      keywords     = {DNA strand breaks (Other) / nonlinear photodamage (Other) /
                      oxidative DNA damage (Other) / reductive DNA damage (Other)
                      / wavelength selectivity (Other)},
      cin          = {W650},
      ddc          = {500},
      cid          = {I:(DE-He78)W650-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37307476},
      doi          = {10.1073/pnas.2220132120},
      url          = {https://inrepo02.dkfz.de/record/276790},
}