title: X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining.
abstract: DNA double-strand breaks (DSBs) are essential intermediates in Ig gene rearrangements: V(D)J and class switch recombination (CSR). In contrast to V(D)J recombination, which is almost exclusively dependent on nonhomologous end joining (NHEJ), CSR can occur in NHEJ-deficient cells via a poorly understand backup pathway (or pathways) often termed alternative end joining (A-EJ). Recently, several components of the single-strand DNA break (SSB) repair machinery, including XRCC1, have been implicated in A-EJ. To determine its role in A-EJ and CSR, Xrcc1 was deleted by targeted mutation in the CSR proficient mouse B-cell line, CH12F3. Here we demonstrate that XRCC1 deficiency slightly increases the efficiency of CSR. More importantly, Lig4 and XRCC1 double-deficient cells switch as efficiently as Lig4-deficient cells, clearly indicating that XRCC1 is dispensable for A-EJ in CH12F3 cells during CSR.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.forename: Weifeng
authors.initials: W
authors.lastname: Mao
authors.forename: Kefei
authors.initials: K
authors.lastname: Yu
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018390:Gene Targeting; D005816:Genetic Complementation Test; D023281:Genomics; D008024:Ligands; D051379:Mice; D008957:Models, Genetic; D013997:Time Factors; D060152:V(D)J Recombination; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D000076105:X-ray Repair Cross Complementing Protein 1; C000619352:Xrcc1 protein, mouse