Nucleotide excision repair (NER) is an essential DNA repair system distinguished
from other such systems by its extraordinary versatility. NER removes a wide
variety of structurally dissimilar lesions having only their bulkiness in
common. NER can also repair several less bulky nucleobase lesions, such as
8-oxoguanine. Thus, how a single DNA repair system distinguishes such a diverse
array of structurally divergent lesions from undamaged DNA has been one of the
great unsolved mysteries in the field of genome maintenance. Here we employ a
synthetic crystallography approach to obtain crystal structures of the pivotal
NER enzyme UvrB in complex with duplex DNA, trapped at the stage of
lesion-recognition. These structures coupled with biochemical studies suggest
that UvrB integrates the ATPase-dependent helicase/translocase and
lesion-recognition activities. Our work also conclusively establishes the
identity of the lesion-containing strand and provides a compelling insight to
how UvrB recognizes a diverse array of DNA lesions.
