Biology subjects

Douki, T.

Publications and source records attributed to Douki, T..

4 recordsLinked to original sources

bioRxiv2026

The Conformation of the Complementary Strand and the Deformation of the DNA Groove upon DDB2 Binding Justifies the Different Repair Rates for Cyclobutane Pyrimidine Dimers.

The repair of photo-induced DNA lesions through nucleotide excision repair machinery is still the source of important questions. It has been observed that the repair rate of the different cyclobutane pyrimidine dimers, i.e. the photoproducts induced by dimerization of two {pi}-stacked pyrimidines (T<>T, T<>C, C<>T, C<>C), depends on the nucleobases involved in the lesion. TT derivatives (T<>T) are removed more slowly than those containing cytosine, especially in 5. Using all-atom molecular dynamics simulations, we demonstrate that the variation of the repair rate observed in human skin and in cultured cutaneous cell may be associated to the recognition of the four lesions by the DDB2 protein moiety, and more specifically by the differential structural deformation induced on the complementary strand and the major groove. These effects may then hamper differentially the downstream recruitment of the repair complexes. The observed DNA deformation correlates with the experimental repair rate and suggests a structural rationale for the different repair rates of CPD by nucleotide excision repair machinery. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/724087v2_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@1c02e6forg.highwire.dtl.DTLVardef@28b3c1org.highwire.dtl.DTLVardef@3143fborg.highwire.dtl.DTLVardef@664d48_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2024

p53 Regulates Nuclear Architecture to Reduce Carcinogen Sensitivity and Mutagenic Potential

The p53 tumor suppressor is an indispensable regulator of DNA damage responses that accelerates carcinogenesis when mutated. In this report, we uncover a new mechanism by which p53 maintains genomic integrity in the absence of canonical DNA damage response activation. Specifically, loss of p53 dramatically alters chromatin structure at the nuclear periphery, allowing increased transmission of an environmental carcinogen, ultraviolet (UV) radiation, into the nucleus. Genome-wide mapping of UV-induced DNA lesions in p53-deficient primary cells reveals elevated lesion abundance in regions corresponding to locations of high mutation burden in malignant melanomas. These findings uncover a novel role of p53 in the suppression of mutations that contribute to cancer and highlight the critical influence of nuclear architecture in regulating sensitivity to carcinogens. One-Sentence SummaryThe p53 tumor suppressor reduces carcinogen sensitivity and mutagenic potential by maintaining nuclear architecture.

cancer biology↗

bioRxiv2021

PROTEOMIC SIGNATURES OF MICROBIAL ADAPTATION TO THE HIGHEST UV -IRRADIATION ON EARTH: LESSONS FROM A SOIL ACTINOBACTERIUM

In the Puna region, the total solar irradiation and the UV incidence is the highest on Earth, thus, restraining the physiology of individual microorganisms and the composition of microbial communities. UV-resistance of microbial strains thriving in High-Altitude Andean Lakes was demonstrated and their mechanisms were partially characterized by genomic analysis, biochemical and physiological assays. In this work, we present the molecular events involved in the adaptive response of the model HAAL extremophilic actinobacterium Nesterenkonia sp. Act20 under artificial UV-B radiation, herein called as UV-resistome. Proteomic profiles of cultures exposed to different UV-experimental conditions showed that the leading systems for adaptation to the UV-challenge in-vitro are DNA repair and antioxidant mechanisms.

molecular biology↗

bioRxiv2020

Photoinduced DNA Lesions in Dormant Bacteria. The Peculiar Route Leading to Spore Photoproduct Unraveled by Multiscale Molecular Dynamics

Some bacterial species enter a dormant state in the form of spores to resist to unfavorable external conditions. Spores are resistant to a wide series of stress agents, including UV radiation, and can last for tens to hundreds of years. Due to the suspension of biological functions such as DNA repair, they accumulate DNA damage upon exposure to UV radiation. Differently from active organisms, the most common DNA photoproduct in spores are not cyclobutane pyrimidine dimers, but rather the so-called spore photoproduct. This non-canonical photochemistry results from the dry state of DNA and the binding to small acid soluble proteins that drastically modify the structure and photoreactivity of the nucleic acid. In this contribution, we use multiscale molecular dynamics simulations including extended classical molecular dynamics and QM/MM biased dynamics to elucidate the coupling of electronic and structural factors leading to this photochemical outcome. In particular, we rationalize the well-described impact of the peculiar DNA environment found in spores on the favored formation of the spore photoproduct, given the small free energy barrier found for this path. Meanwhile, the specific organization of spore DNA precludes the photochemical path leading to cyclobutane pyrimidine dimers formation. TOC GRAPHICS O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

biophysics↗