title: ATMIN is required for maintenance of genomic stability and suppression of B cell lymphoma.
abstract: Defective V(D)J rearrangement of immunoglobulin heavy or light chain (IgH or IgL) or class switch recombination (CSR) can initiate chromosomal translocations. The DNA-damage kinase ATM is required for the suppression of chromosomal translocations but ATM regulation is incompletely understood. Here, we show that mice lacking the ATM cofactor ATMIN in B cells (ATMIN(ΔB/ΔB)) have impaired ATM signaling and develop B cell lymphomas. Notably, ATMIN(ΔB/ΔB) cells exhibited defective peripheral V(D)J rearrangement and CSR, resulting in translocations involving the Igh and Igl loci, indicating that ATMIN is required for efficient repair of DNA breaks generated during somatic recombination. Thus, our results identify a role for ATMIN in regulating the maintenance of genomic stability and tumor suppression in B cells.
authors.affiliation: Mammalian Genetics Lab, Cancer Research UK, London Research Institute, 44, Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Joanna I
authors.initials: JI
authors.lastname: Loizou
authors.forename: Rocio
authors.initials: R
authors.lastname: Sancho
authors.forename: Nnennaya
authors.initials: N
authors.lastname: Kanu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Bolland
authors.forename: Fengtang
authors.initials: F
authors.lastname: Yang
authors.forename: Cristina
authors.initials: C
authors.lastname: Rada
authors.forename: Anne E
authors.initials: AE
authors.lastname: Corcoran
authors.forename: Axel
authors.initials: A
authors.lastname: Behrens
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D053960:DNA Breaks; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D050438:Genes, Immunoglobulin Heavy Chain; D050439:Genes, Immunoglobulin Light Chain; D042822:Genomic Instability; D017578:Immunoglobulin Class Switching; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011995:Recombination, Genetic; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C554480:ATMIN protein, mouse; D018941:Antigens, CD19; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases