Nucleotide excision repair (NER) is a universal DNA repair mechanism found
in all three kingdoms of life. Its ability to repair a broad range of DNA l
esions sets NER apart From other repair mechanisms. NER systems recognize t
he damaged DNA strand and cleave it 3', then 5' to the lesion. After the ol
igonucleotide containing the lesion is removed, repair synthesis fills the
resulting gap. UvrB is the central component of bacterial NER. It is direct
ly involved in distinguishing damaged from undamaged DNA and guides the DNA
from recognition to repair synthesis. Recently solved structures of UvrB f
rom different organisms represent the first high-resolution view into bacte
rial NER. The structures provide detailed insight into the domain architect
ure of UvrB and, through comparison, suggest possible domain movements. The
structure of UvrB consists of five domains. Domains la and 3 bind ATP at t
he inter-domain interface and share high structural similarity to helicases
of superfamilies I and II. Not related to helicase structures, domains 2 a
nd 4 are involved in interactions with either UvrA or UvrC, whereas domain
Ib was implicated for DNA binding. The structures indicate that ATP binding
and hydrolysis is associated with domain motions. UvrB's ATPase activity,
however, is not coupled to the separation of long DNA duplexes as in helica
ses, but rather leads to the formation of the preincision complex with the
damaged DNA substrate. The location of conserved residues and structural co
mparisons with helicase-DNA structures suggest how UvrB might bind to DNA.
A model of the UvrB-DNA interaction in which a beta-hairpin of UvrB inserts
between the DNA double strand has been proposed recently. This padlock mod
el is developed further to suggest two distinct consequences of domain moti
on: in the UvrA(2)B-DNA complex, domain motions lead to translocation along
the DNA, whereas in the tight UvrB-DNA pre-incision complex, they lead to
distortion of the 3' incision site. (C) 2000 Elsevier Science B.V. All righ
ts reserved.