Figure 4. MMR response to genomic 5-FU.
5-FU:A pairs that arise upon incorporation of FdUTP into the genome during DNA synthesis are recognized and processed by the BER pathway (left; see text and Figure 3 for details). 5-FU:G pairs, however, are recognized by the MMR MutSa complex comprised of MSH2:MHS6 (right). Subsequently, the MutLα heterdimer made up of MLH1:PMS2 associates and either initiates a repair response or triggers apoptotic signaling through ATR/CHK1 activation. A burning question that remains though is “how do 5-FU:G mispairs arise in chromosomal DNA?” See text for further details.