title: Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2.
abstract: 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.
authors.affiliation: Genetics Program, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Min
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Rothlein
authors.forename: Carol E
authors.initials: CE
authors.lastname: Schrader
authors.forename: Janet
authors.initials: J
authors.lastname: Stavnezer
authors.forename: Erik
authors.initials: E
authors.lastname: Selsing
mesh_terms: 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
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein