Structural dynamics and interactions of Xeroderma pigmentosum complementation group A (XPA98–210) with damaged DNA

Nucleotide excision repair (NER) in higher organisms repair massive DNA abrasions caused by ultraviolet rays, and various mutagens, where Xeroderma pigmentosum group A (XPA) protein is known to be involved in damage recognition step. Any mutations in XPA cause classical Xeroderma pigmentosum disease. The extent to which XPA is required in the NER is still unclear. Here, we present the comparative study on the structural and conformational changes in globular DNA binding domain of XPA98–210 in DNA bound and DNA free state. Atomistic molecular dynamics simulation was carried out for both XPA98–210 systems using AMBER force fields. We observed that XPA98–210 in presence of damaged DNA exhibited more structural changes compared to XPA98–210 in its free form. When XPA is in contact with DNA, we found marked stability of the complex due to the formation of characteristic longer antiparallel β-sheets consisting mainly lysine residues.