title: Converting a DNA damage checkpoint effector (UmuD2C) into a lesion bypass polymerase (UmuD'2C).
abstract: During the SOS response of Escherichia coli to DNA damage, the umuDC operon is induced, producing the trimeric protein complexes UmuD2C, a DNA damage checkpoint effector, and UmuD'2C (DNA polymerase V), which carries out translesion synthesis, the basis of 'SOS mutagenesis'. UmuD'2, the homodimeric component of DNA pol V, is produced from UmuD by RecA-facilitated self-cleavage, which removes the 24 N-terminal residues of UmuD. We report the solution structure of UmuD'2 (PDB ID 1I4V) and interactions within UmuD'-UmuD, a heterodimer inactive in translesion synthesis. The overall shape of UmuD'2 in solution differs substantially from the previously reported crystal structure, even though the topologies of the two structures are quite similar. Most significantly, the active site residues S60 and K97 do not point directly at one another in solution as they do in the crystal, suggesting that self-cleavage of UmuD might require RecA to assemble the active site. Structural differences between UmuD'2 and UmuD'- UmuD suggest that UmuD'2C and UmuD2C might achieve their different biological activities through distinct interactions with RecA and DNA pol III.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Ferentz
authors.forename: G C
authors.initials: GC
authors.lastname: Walker
authors.forename: G
authors.initials: G
authors.lastname: Wagner
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D029968:Escherichia coli Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C120926:DNA polymerase V, E coli; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli