One result of aberrant DNA repair is genomic instability. We constructed a knockin mouse with a hypomorphic mutant of POLB. Unlike mice completely deleted of POLB, our mice survived past birth but are quite small.
We used the Cre-Lox system of conditional gene targeting to specifically delete the POLB gene from the germline of the mouse. Deletion of POLB leads to defects in Prophase I of meiosis.
There are over 150 SNPs in DNA repair genes that are predicted to affect function and more are being identified each day through DNA sequencing projects including 1000 Genomes. In addition, there are SNPs in noncoding regions of the DNA repair genes and their functions remain largely unknown.
DNA polymerases catalyze nucleotidyl transfer and have the capacity to select the correct nucleotide for incorporation into DNA. We are interested in the mechanism by which DNA polymerases select the correct nucleotide. Our model DNA polymerase is DNA polymerase beta (Pol ß).