Nucleotide excision repair (NER) is the primary mechanism to remove large covalent DNA lesions resulting from exposure to a wide variety of genotoxic agents.  The human NER mechanism is dependent on the coordinated activity of over thirty proteins that build a series of protein machines to repair the damaged DNA.  Two proteins, XPC and XPA, play critical roles in NER despite lacking any enzymatic activity.  XPC serves as a generic sensor of damaged DNA, marking a site for repair and initiating assembly of the NER machinery. XPA is generally believed to act as a molecular scaffold upon which the NER machines are built.  Previous studies have suggested a weak but direct physical interaction between XPC and XPA, and genetic evidence suggests this interaction may aid in recruitment of XPA to potential damage sites in cells.  In this study, we identified a novel protein complex between human XPA and the globular transglutaminase-like domain of XPC (XPC-TGD). We employed a chemical cross-linking strategy to isolate protein complexes formed from highly purified recombinant proteins.  Complexes were purified by SDS-PAGE and subjected to trypsin proteolysis. MALDI-TOF mass spectrometry analysis identified polypeptide fragments from both the XPA and XPC proteins in tryptic digests of isolated complex samples.  These results suggest the XPA may interact with XPC by binding to the XPC-TGD during assembly of the NER machinery.  <br/>

Isolation of a novel compex between human NER proteins XPC and XPA

2019 Spring National Meeting

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