Model for MMR resolution of AID-generated dU:G mispairs.
2010-06-17T01:34:49Z (GMT) by
<p>In the DNA deamination model, MSH2/MSH6 recognizes the initial AID-generated dU:G lesion, the damaged strand is excised by Exo1, and Polη is preferentially recruited to the nontranscribed strand (NTS) to generate mutations at A sites within W<u>A</u> motifs. Fewer T sites within <u>T</u>W motifs are mutated, contributing to the singular A≫T and W<u>A</u>≫<u>T</u>W biases that characterize SHM and reflect the reduced targeting of A sites by Polη in the transcribed strand (TS). We highlight here the error-free repair effect of MMR at the dU:G mispairs within the excised patch, which is revealed in <i>Msh2<sup>−/−</sup>Msh6<sup>−/−</sup></i> mice by a significant increase in unrepaired dU:G lesions that are replicated as transitions at C:G sites in WR<u>C</u>/<u>G</u>YW hotspots (i.e. C-to-T within WR<u>C</u> in the NTS, and G-to-A within <u>G</u>YW as a reflection of C-to-T mutations in the TS).</p>