2Institute for Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia
3Novosibirsk State University, 630090 Novosibirsk, Russia
4Altai State University, 656049 Barnaul, Russia
* To whom correspondence should be addressed.
Received August 27, 2014; Revision received October 10, 2014
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.
KEY WORDS: nucleotide excision repair, bulky DNA lesions, clustered DNA lesions, DNA–protein complexes, Y-box binding protein 1 (YB-1), XPC-HR23B