title: Y-box binding protein 1 (YB-1) promotes detection of DNA bulky lesions by XPC-HR23B factor.
abstract: The nucleotide excision repair system (NER) is one of the main mechanisms protecting cellular DNA from lesions caused by such significant environmental factors as UV radiation, the influence of polycyclic aromatic hydrocarbons, and medical treatment by several antitumor drugs, e.g. cisplatin. One of the major NER components is XPC-HR23B, the key factor during the damage recognition step of repair. Binding of XPC-HR23B to DNA that contains different bulky lesions impairing the structure of DNA is the basis for the wide substrate specificity of this DNA repair pathway. The multifunctional protein YB-1 among other protein factors has high affinity towards damaged DNA. Involvement of YB-1 in the cellular response to genotoxic stress and its ability to interact with damaged DNA harboring lesions of various origins pinpoint its putative involvement as a modulatory factor in DNA damage recognition and verification steps of NER. In the present work, we assayed functional interactions of protein factors XPC-HR23B and YB-1 upon binding to DNA structures mimicking damaged DNA containing single bulky lesions, as substrates of NER, and bulky lesions combined with abasic sites as an example of clustered lesions. The results indicate that YB-1 and XPC-HR23B stimulate each other in binding to DNA containing a bulky or clustered lesion, which suggests the involvement of YB-1 in the regulation of DNA repair by the NER mechanism.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, 630090, Russia. lavrik@niboch.nsc.ru.
authors.forename: E E
authors.initials: EE
authors.lastname: Fomina
authors.forename: P E
authors.initials: PE
authors.lastname: Pestryakov
authors.forename: E A
authors.initials: EA
authors.lastname: Maltseva
authors.forename: I O
authors.initials: IO
authors.lastname: Petruseva
authors.forename: D A
authors.initials: DA
authors.lastname: Kretov
authors.forename: L P
authors.initials: LP
authors.lastname: Ovchinnikov
authors.forename: O I
authors.initials: OI
authors.lastname: Lavrik
mesh_terms: D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D013379:Substrate Specificity; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; C513287:RAD23B protein, human; D051840:Y-Box-Binding Protein 1; C086984:XPC protein, human; D004247:DNA; D045643:DNA Repair Enzymes