Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2.
The mechanisms that target class switch recombination (CSR) to antibody gene switch (S) regions are unknown. Analyses of switch site locations in wild-type mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4-5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for switching independent of Smu sequences. This CSR-accessible domain is reminiscent of the promoter-defined domains that target somatic hypermutation. Within the 4-5-kb CSR domain, the targeting of S site locations also depends on the Msh2 mismatch repair protein because Msh2-deficient mice show an increased focus of sites to the Smu tandem repeat region. We propose that Msh2 affects S site location because sequences with few activation-induced cytidine deaminase targets generate mostly switch DNA cleavages that require Msh2-directed processing to allow CSR joining.
Min
Irene M
IM
Genetics Program, Tufts University School of Medicine, Boston, MA 02111, USA.
Rothlein
Lisa R
LR
Schrader
Carol E
CE
Stavnezer
Janet
J
Selsing
Erik
E
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D051718:MutS Homolog 2 Protein; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020080:Tandem Repeat Sequences / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein