Recognition and removal of clustered DNA lesions via nucleotide excision repair Full article
| Journal |
DNA Repair
ISSN: 1568-7864 |
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| Output data | Year: 2021, Volume: 108, Article number : 103225, Pages count : DOI: 10.1016/j.dnarep.2021.103225 | ||
| Tags | Nucleotide excision repair; Higher eukaryote; Clustered DNA lesions; Multiple DNA lesions; Molecular dynamics | ||
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Abstract:
Clustered damage of DNA consists of two or more lesions located within one or two turns of the DNA helix. Clusters consisting of lesions of various structures can arise under the influence of strong damaging factors, especially if the cells have a compromised repair status. In this work, we analyzed how the presence of an analog of the apurinic/apyrimidinic site - a non-nucleoside residue consisting of diethylene glycol phosphodiester (DEG) - affects the recognition and removal of a bulky lesion (a non-nucleoside site of the modified DNA strand containing a fluorescein residue, nFlu) from DNA by a mammalian nucleotide excision repair system. Here we demonstrated that the efficiency of nFlu removal decreases in the presence of DEG in the complementary strand and is completely suppressed when the DEG is located opposite the nFlu. By contrast, protein factor XPCRAD23B, which initiates global genomic nucleotide excision repair, has higher affinity for DNA containing clustered damage as compared to DNA containing a single bulky lesion; the affinity of XPC strengthens as the positions of DEG and nFlu become closer. The changes in the double-stranded DNA's geometry caused by the presence of clustered damage were also assessed. The obtained experimental data together with the results of molecular dynamics simulations make it possible to get insight into the structural features of DNA containing clustered lesions that determine the efficiency of repair. Speaking more broadly, this study should help to understand the probable fate of bulky adduct-containing clusters of various topologies in the mammalian cell.
Cite:
Naumenko N.
, Petruseva I.O.
, Lomzov A.A.
, Lavrik O.
Recognition and removal of clustered DNA lesions via nucleotide excision repair
DNA Repair. 2021. V.108. 103225 . DOI: 10.1016/j.dnarep.2021.103225 WOS Scopus РИНЦ OpenAlex
Recognition and removal of clustered DNA lesions via nucleotide excision repair
DNA Repair. 2021. V.108. 103225 . DOI: 10.1016/j.dnarep.2021.103225 WOS Scopus РИНЦ OpenAlex
Dates:
| Published print: | Sep 10, 2021 |
Identifiers:
| Web of science: | WOS:000704000300004 |
| Scopus: | 2-s2.0-85115420423 |
| Elibrary: | 47088303 |
| OpenAlex: | W3200124510 |