Structural dynamics and interactions of Xeroderma pigmentosum complementation group A (XPA_98–210) with damaged DNA

Abstract

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 XPA_98–210 in DNA bound and DNA free state. Atomistic molecular dynamics simulation was carried out for both XPA_98–210 systems using AMBER force fields. We observed that XPA_98–210 in presence of damaged DNA exhibited more structural changes compared to XPA_98–210 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.

Keywords:

• nucleotide excision repair
• Xeroderma pigmentosum disease
• molecular dynamics

Acknowledgements

We would like to extend our deepest gratitude to Tezpur University for the research grant. We would also like to express our appreciation and thankfulness to DBT funded Bioinformatics Infrastructure facility in the Department of Molecular Biology and Biotechnology at Tezpur University for providing us with all the required computational facility to conduct this research work.