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Interactions between UvrA and UvrB: the role of UvrB's domain 2 in nucleotide excision repair
Author(s) -
Truglio James J,
Croteau Deborah L,
Skorvaga Milan,
DellaVecchia Matthew J,
Theis Karsten,
Mandavilli Bhaskar S,
Van Houten Bennett,
Kisker Caroline
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600263
Subject(s) - biology , nucleotide excision repair , nucleotide , genetics , pyrimidine dimer , microbiology and biotechnology , dna repair , dna , gene
Nucleotide excision repair (NER) is a highly conserved DNA repair mechanism present in all kingdoms of life. UvrB is a central component of the bacterial NER system, participating in damage recognition, strand excision and repair synthesis. None of the three presently available crystal structures of UvrB has defined the structure of domain 2, which is critical for the interaction with UvrA. We have solved the crystal structure of the UvrB Y96A variant, which reveals a new fold for domain 2 and identifies highly conserved residues located on its surface. These residues are restricted to the face of UvrB important for DNA binding and may be critical for the interaction of UvrB with UvrA. We have mutated these residues to study their role in the incision reaction, formation of the pre‐incision complex, destabilization of short duplex regions in DNA, binding to UvrA and ATP hydrolysis. Based on the structural and biochemical data, we conclude that domain 2 is required for a productive UvrA–UvrB interaction, which is a pre‐requisite for all subsequent steps in nucleotide excision repair.