xeroderma 
 pigmentosum complementation group a ( xpa ) protein plays 
 a critical role in the repair of dna damage via the nucleotide excision 
 repair ( ner ) pathway . 
 xpa serves as a scaffold for ner , interacting 
 with several other ner proteins as well as the dna substrate . 
 the 
 critical importance of xpa is underscored by its association with 
 the most severe clinical phenotypes of the genetic disorder xeroderma 
 pigmentosum . 
 many of these disease - associated mutations map to the 
 xpa98219 dna - binding domain ( dbd ) first reported 
 20 years ago . 
 although multiple solution nmr structures of 
 xpa98219 have been determined , the molecular basis 
 for the interaction of this domain with dna is only poorly characterized . 
 in this report , we demonstrate using a fluorescence anisotropy dna - binding 
 assay that the previously reported xpa dbd binds dna with substantially 
 weaker affinity than the full - length protein . in - depth analysis of 
 the xpa sequence suggested that the original dbd construct lacks critical 
 basic charge and helical elements at its c - terminus . 
 generation and 
 analysis of a series of c - terminal extensions beyond residue 219 yielded 
 a stable , soluble human xpa98239 construct that 
 binds to a y - shaped ssdna 
 dsdna junction and other substrates 
 with the same affinity as the full - length protein . 
 two - dimensional 15n1h nmr suggested xpa98239 contains the same globular core as xpa98219 and 
 likely undergoes a conformational change upon binding dna . 
 together , 
 our results demonstrate that the xpa dbd should be redefined and that 
 xpa98239 is a suitable model to examine the dna 
 binding activity of human xpa .