DNA-HISTONE CROSS-LINKS: FORMATION AND REPAIR

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dc.contributor.authorPachva, Manideep C.
dc.contributor.authorKisselev, Alexei F.
dc.contributor.authorMatkarimov, Bakhyt T.
dc.contributor.authorSaparbaev, Murat
dc.contributor.authorGroisman, Regina
dc.date.accessioned2021-01-25T05:23:30Z
dc.date.available2021-01-25T05:23:30Z
dc.date.issued2020-12-21
dc.description.abstractThe nucleosome is a stretch of DNA wrapped around a histone octamer. Electrostatic interactions and hydrogen bonds between histones and DNA are vital for the stable organization of nucleosome core particles, and for the folding of chromatin into more compact structures, which regulate gene expression via controlled access to DNA. As a drawback of tight association, under genotoxic stress, DNA can accidentally crosslink to histone in a covalent manner, generating a highly toxic DNA-histone cross-link (DHC). DHC is a bulky lesion that can impede DNA transcription, replication, and repair, often with lethal consequences. The chemotherapeutic agent cisplatin, as well as ionizing and ultraviolet irradiations and endogenously occurring reactive aldehydes, generate DHCs by forming either stable or transient covalent bonds between DNA and side-chain amino groups of histone lysine residues. The mechanisms of DHC repair start to unravel, and certain common principles of DNA-protein cross-link (DPC) repair mechanisms that participate in the removal of cross-linked histones from DNA have been described. In general, DPC is removed via a two-step repair mechanism. First, cross-linked proteins are degraded by specific DPC proteases or by the proteasome, relieving steric hindrance. Second, the remaining DNA-peptide cross-links are eliminated in various DNA repair pathways. Delineating the molecular mechanisms of DHC repair would help target specific DNA repair proteins for therapeutic intervention to combat tumor resistance to chemotherapy and radiotherapy.en_US
dc.identifier.citationPachva, M. C., Kisselev, A. F., Matkarimov, B. T., Saparbaev, M., & Groisman, R. (2020). DNA-histone cross-links: Formation and repair. Frontiers in Cell and Developmental Biology, 8, 607045.en_US
dc.identifier.issn2296-634X
dc.identifier.urihttps://www.frontiersin.org/articles/10.3389/fcell.2020.607045/full
dc.identifier.urihttps://doi.org/10.3389/fcell.2020.607045
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/5232
dc.language.isoenen_US
dc.publisherFrontiers Mediaen_US
dc.relation.ispartofseriesFrontiers in Cell and Developmental Biology;
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectDNA-histone cross-linken_US
dc.subjectnucleosome core particleen_US
dc.subjectchromatinen_US
dc.subjectgenome instabilityen_US
dc.subjectspartan proteaseen_US
dc.subjectproteasomeen_US
dc.subjectDNA repairen_US
dc.subjectResearch Subject Categories::NATURAL SCIENCES::Biologyen_US
dc.titleDNA-HISTONE CROSS-LINKS: FORMATION AND REPAIRen_US
dc.typeArticleen_US
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