title: The Smu tandem repeat region is critical for Ig isotype switching in the absence of Msh2.
abstract: Deficiencies of the Msh2 protein or the Smu tandem repeat (SmuTR) sequences each reduce isotype switching in mice by about 2- to 3-fold. We find that switching in mice deficient for both Msh2 and SmuTR is nearly ablated. We propose that the SmuTR provides closely spaced cleavage sites that can undergo switch recombination independent of Msh2, whereas cleavages in sequences flanking the SmuTR require Msh2 processing to allow recombinational joining. We also find that changes in Smu sequences alter the focus of switch junctions within Sgamma sequences, indicating that sequences of switch regions act together in the choice of switch recombination junctions. These findings help to explain the conservation of tandemly repeated switch regions associated with heavy chain constant genes in species capable of switching.
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: Carol E
authors.initials: CE
authors.lastname: Schrader
authors.forename: Joycelyn
authors.initials: J
authors.lastname: Vardo
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Luby
authors.forename: Nicole
authors.initials: N
authors.lastname: D'Avirro
authors.forename: Janet
authors.initials: J
authors.lastname: Stavnezer
authors.forename: Erik
authors.initials: E
authors.lastname: Selsing
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D007132:Immunoglobulin Isotypes / Q000378:metabolism*; D007438:Introns / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D051718:MutS Homolog 2 Protein; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D020080:Tandem Repeat Sequences
chemical_list: D004268:DNA-Binding Proteins; D007132:Immunoglobulin Isotypes; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein