Ectopic restriction of DNA repair reveals that UNG2 excises AID-induced uracils predominantly or exclusively during G1 phase

As revealed using an UNG2 inhibitor peptide fused to cell cycle–regulated degradation motifs, the cell cycle phase during which uracil residues are processed determines the fidelity of repair.

[1]  R. Maul,et al.  XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in Igh genes , 2011, The Journal of experimental medicine.

[2]  H. Krokan,et al.  Uracil-DNA Glycosylase in Base Excision Repair and Adaptive Immunity , 2011, The Journal of Biological Chemistry.

[3]  C. Jolly,et al.  Incorporation of dUTP does not mediate mutation of A:T base pairs in Ig genes in vivo , 2010, Nucleic acids research.

[4]  D. Nicolae,et al.  Somatic hypermutation: Processivity of the cytosine deaminase AID and error-free repair of the resulting uracils , 2009, Cell cycle.

[5]  N. Maizels,et al.  Temporal Regulation of Ig Gene Diversification Revealed by Single-Cell Imaging1 , 2009, The Journal of Immunology.

[6]  C. E. Schrader,et al.  Mechanism and regulation of class switch recombination. , 2008, Annual review of immunology.

[7]  Sergio Roa,et al.  The biochemistry of somatic hypermutation. , 2008, Annual review of immunology.

[8]  J. Manis,et al.  Fixing DNA breaks during class switch recombination , 2008, The Journal of experimental medicine.

[9]  D. Schatz,et al.  Two levels of protection for the B cell genome during somatic hypermutation , 2008, Nature.

[10]  Atsushi Miyawaki,et al.  Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression , 2008, Cell.

[11]  O. Jensen,et al.  Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and association with RPA , 2007, The EMBO journal.

[12]  M. Neuberger,et al.  Dependence of antibody gene diversification on uracil excision , 2007, The Journal of experimental medicine.

[13]  C. E. Schrader,et al.  APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination , 2007, The Journal of Experimental Medicine.

[14]  E. Selsing,et al.  Activation-Induced Cytidine Deaminase-Dependent DNA Breaks in Class Switch Recombination Occur during G1 Phase of the Cell Cycle and Depend upon Mismatch Repair1 , 2007, The Journal of Immunology.

[15]  J. Carulli,et al.  Inflammatory arthritis can be reined in by CpG-induced DC–NK cell cross talk , 2007, The Journal of experimental medicine.

[16]  J. Stavnezer,et al.  DNA polymerase β is able to repair breaks in switch regions and plays an inhibitory role during immunoglobulin class switch recombination , 2007, The Journal of experimental medicine.

[17]  M. Neuberger,et al.  Molecular mechanisms of antibody somatic hypermutation. , 2007, Annual review of biochemistry.

[18]  Jason G. Cyster,et al.  Imaging of Germinal Center Selection Events During Affinity Maturation , 2007, Science.

[19]  F. Delbos,et al.  DNA polymerase η is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse , 2007, The Journal of experimental medicine.

[20]  D. Nicolae,et al.  Somatic Hypermutation and Class Switch Recombination in Msh6−/−Ung−/− Double-Knockout Mice1 , 2006, The Journal of Immunology.

[21]  M. Neuberger,et al.  The in vivo pattern of AID targeting to immunoglobulin switch regions deduced from mutation spectra in msh2 −/− ung −/− mice , 2006, The Journal of experimental medicine.

[22]  N. de Wind,et al.  Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice , 2006, The Journal of experimental medicine.

[23]  M. Neuberger,et al.  SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation versus repair , 2006, The EMBO journal.

[24]  Jeff Holst,et al.  Generation of T-cell receptor retrogenic mice , 2006, Nature Protocols.

[25]  D. Barnes,et al.  C → T mutagenesis and γ‐radiation sensitivity due to deficiency in the Smug1 and Ung DNA glycosylases , 2005, The EMBO journal.

[26]  N. Maizels,et al.  The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions , 2005, Nature Immunology.

[27]  C. Lawrence,et al.  An update on the role of translesion synthesis DNA polymerases in Ig hypermutation. , 2005, Trends in immunology.

[28]  M. Neuberger,et al.  Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. , 2004, Molecular cell.

[29]  F. Alt,et al.  Replication protein A interacts with AID to promote deamination of somatic hypermutation targets , 2004, Nature.

[30]  J. A. Fischer,et al.  Proteolytic degradation of the nuclear isoform of uracil-DNA glycosylase occurs during the S phase of the cell cycle. , 2004, DNA repair.

[31]  R. Brink,et al.  Reduced Switching in SCID B Cells Is Associated with Altered Somatic Mutation of Recombined S Regions 1 , 2003, The Journal of Immunology.

[32]  A. Fischer,et al.  Human uracil–DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination , 2003, Nature Immunology.

[33]  D. Kitamura,et al.  RAG2 Is Down-regulated by Cytoplasmic Sequestration and Ubiquitin-dependent Degradation* , 2002, The Journal of Biological Chemistry.

[34]  F. Skorpen,et al.  hUNG2 Is the Major Repair Enzyme for Removal of Uracil from U:A Matches, U:G Mismatches, and U in Single-stranded DNA, with hSMUG1 as a Broad Specificity Backup* , 2002, The Journal of Biological Chemistry.

[35]  M. Neuberger,et al.  Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase , 2002, Nature.

[36]  B. Bertocci,et al.  AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line , 2002, Nature Immunology.

[37]  B. Corneo,et al.  A short peptide at the C terminus is responsible for the nuclear localization of RAG2 , 2002, European journal of immunology.

[38]  福嶋 徹 Genetic analysis of the DNA-dependent protein kinase reveals an inhibitory role of Ku in late S-G2 phase DNA double-strand break repair , 2002 .

[39]  Thomas Ried,et al.  AID is required to initiate Nbs1/γ-H2AX focus formation and mutations at sites of class switching , 2001, Nature.

[40]  T. Honjo,et al.  Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme , 2000, Cell.

[41]  T. Lindahl,et al.  Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication. , 2000, Molecular cell.

[42]  P. Hodgkin,et al.  Switching to IgG3, IgG2b, and IgA is division linked and independent, revealing a stochastic framework for describing differentiation. , 1999, Journal of immunology.

[43]  M. Otterlei,et al.  Post‐replicative base excision repair in replication foci , 1999, The EMBO journal.

[44]  J. Swenberg,et al.  Endogenous apurinic/apyrimidinic sites in genomic DNA of mammalian tissues. , 1999, Cancer research.

[45]  D. Lilley,et al.  DNA Repair , 1998, Nucleic Acids and Molecular Biology.

[46]  S. Desiderio,et al.  A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. , 1996, Immunity.

[47]  T. Hunt,et al.  The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase. , 1996, The EMBO journal.

[48]  A. B. Lyons,et al.  B cell differentiation and isotype switching is related to division cycle number , 1996, The Journal of experimental medicine.

[49]  J. Tainer,et al.  Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: Protein mimicry of DNA , 1995, Cell.

[50]  T. Hunter,et al.  The differential localization of human cyclins A and B is due to a cytoplasmic retention signal in cyclin B. , 1994, The EMBO journal.

[51]  G. Dianov,et al.  Generation of single-nucleotide repair patches following excision of uracil residues from DNA , 1992, Molecular and cellular biology.

[52]  E. Nigg,et al.  Cyclin B2 undergoes cell cycle-dependent nuclear translocation and, when expressed as a non-destructible mutant, causes mitotic arrest in HeLa cells , 1992, The Journal of cell biology.

[53]  Z. Livneh,et al.  Bypass and termination at apurinic sites during replication of single-stranded DNA in vitro: a model for apurinic site mutagenesis. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[54]  W. Wooster,et al.  Crystal structure of , 2005 .

[55]  C. E. Schrader,et al.  APE 1-and APE 2-dependent DNA breaks in immunoglobulin class switch recombination , 2022 .