Structural and mutational analyses of Deinococcus radiodurans UvrA2 provide insight into DNA binding and damage recognition by UvrAs.
UvrA proteins are key actors in DNA damage repair and play an essential role in prokaryotic nucleotide excision repair (NER), a pathway that is unique in its ability to remove a broad spectrum of DNA lesions. Understanding the DNA binding and damage recognition activities of the UvrA family is a critical component for establishing the molecular basis of this process. Here we report the structure of the class II UvrA2 from Deinococcus radiodurans in two crystal forms. These structures, coupled with mutational analyses and comparison with the crystal structure of class I UvrA from Bacillus stearothermophilus, suggest a previously unsuspected role for the identified insertion domains of UvrAs in both DNA binding and damage recognition. Taken together, the available information suggests a model for how UvrA interacts with DNA and thus sheds new light on the molecular mechanisms underlying the role of UvrA in the early steps of NER.
Timmins
Joanna
J
European Synchrotron Radiation Facility, 38043 Grenoble, France.
Gordon
Elspeth
E
Caria
Sofia
S
Leonard
Gordon
G
Acajjaoui
Samira
S
Kuo
Mei-Shiue
MS
Monchois
Vincent
V
McSweeney
Sean
S
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D003460:Crystallization; D004249:DNA Damage; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D034301:Deinococcus / Q000201:enzymology*; D019281:Dimerization; D001411:Geobacillus stearothermophilus / Q000201:enzymology; D006868:Hydrolysis; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D013997:Time Factors
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases