Interactions between UvrA and UvrB: the role of UvrB's domain 2 in nucleotide excision repair

AUTOR(ES)

Truglio, James J

FONTE

Nature Publishing Group

RESUMO

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.

Documentos Relacionados

• Isolation and Genetic Analysis of Amber uvrA and uvrB Mutants
• Crystal structure of the DNA nucleotide excision repair enzyme UvrB from Thermus thermophilus
• UvrA and UvrB suppress illegitimate recombination: Synergistic action with RecQ helicase
• Architecture of nucleotide excision repair complexes: DNA is wrapped by UvrB before and after damage recognition
• Mutations in the Escherichia coli UvrB ATPase motif compromise excision repair capacity.