Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination.
Isotype switching involves a region-specific, nonhomologous recombinational deletion that has been suggested to occur by nonhomologous joining of broken DNA ends. Here, we find increased donor/acceptor homology at switch junctions from PMS2-deficient mice and propose that class switching can occur by microhomology-mediated end-joining. Interestingly, although isotype switching and somatic hypermutation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nucleotide substitutions generated during somatic hypermutation. This finding is in contrast to MSH2 deficiency. With MSH2, the altered pattern of switch recombination and hypermutation suggests parallels in the mechanics of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may reflect differences in the pathways of break resolution.
Ehrenstein
M R
MR
Department of Medicine, University College London, London W1T 4NJ, United Kingdom. m.ehrenstein@ucl.ac.uk
Rada
C
C
Jones
A M
AM
Milstein
C
C
Neuberger
M S
MS
D000251:Adenosine Triphosphatases / Q000172:deficiency* / Q000235:genetics*; D000818:Animals; D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D017578:Immunoglobulin Class Switching; D051379:Mice; D018345:Mice, Knockout; D000070976:Mismatch Repair Endonuclease PMS2; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C499533:Pms2 protein, mouse; D000070976:Mismatch Repair Endonuclease PMS2; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes