3OSP: Structure Of Rev1

Abasic (apurinic/apyrimidinic) sites are among the most abundant DNA lesions in humans, and they present a strong block to replication. They are also highly mutagenic because when replicative DNA polymerases manage to insert a nucleotide opposite the lesion, they prefer to insert an A. Rev1, a member of Y-family DNA polymerases, does not obey the A-rule. This enzyme inserts a C opposite an abasic lesion with much greater catalytic efficiency than an A, G, or T. We present here the structure of yeast Rev1 in ternary complex with DNA containing an abasic lesion and with dCTP as the incoming nucleotide. The structure reveals a mechanism of synthesis across an abasic lesion that differs from that in other polymerases. The lesion is driven to an extrahelical position, and the incorporation of a C is mediated by an arginine (Arg324) that is conserved in all known orthologs of Rev1, including humans. The hydrophobic cavity that normally accommodates the unmodified G is instead filled with water molecules. Since Gs are especially prone to depurination through a spontaneous hydrolysis of the glycosidic bond, the ability of Rev1 to stabilize an abasic lesion in its active site and employ a surrogate arginine to incorporate a C provides a unique means for the "error-free" bypass of this noninstructional lesion.
PDB ID: 3OSPDownload
MMDB ID: 89852
PDB Deposition Date: 2010/9/9
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3OSP: trimeric; determined by author and by software (PISA)
Molecular Components in 3OSP
Label Count Molecule
Protein (1 molecule)
DNA Repair Protein Rev1(Gene symbol: REV1)
Molecule annotation
Nucleotides(2 molecules)
5'-d(*tp*ap*ap*(3dr)p*gp*tp*ap*gp*gp*gp*gp*ap*gp*gp*ap*t)- 3'
Molecule annotation
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB