Volume 114, Issue 3, Pages 359-370 (August 2003) Histone H2AX  Craig H. Bassing, Heikyung Suh, David O. Ferguson, Katrin F. Chua, John Manis, Mark Eckersdorff, Megan Gleason, Rodrick Bronson, Charles Lee, Frederick W. Alt  Cell  Volume 114, Issue 3, Pages 359-370 (August 2003) DOI: 10.1016/S0092-8674(03)00566-X

Figure 1 Effects of p53 Deficiency on Survival of HΔ/Δ and H+/Δ Mice (A) p53 deficiency does not affect early viability of H2AX-deficient mice. Shown is the expected and actual number of relevant offspring from H+/Δp53+/− crosses. (B) Kapplan-Meier curve representing the percent survival of H+/+P+/+ (n = 9), H+/+P−/− (n = 21), H+/ΔP−/− (n = 29), and HΔ/ΔP−/− (n = 17) cohort mice versus age in days. Cell 2003 114, 359-370DOI: (10.1016/S0092-8674(03)00566-X)

Figure 2 HΔ/ΔP−/−, H+/ΔP−/−, and HΔ/Δ Thymic Lymphomas Harbor Clonal, Complex Translocations (A–D) SKY images of a metaphase from H+/ΔP−/− thymic lymphoma 609 with C9;16;13, C12;9, C2;1, and C1;2 translocations (A) and images of representative translocations C11;10;1 (left) and C11;5;1 (right) from HΔ/ΔP−/− thymic lymphoma 634 (B), C10;11;18 (left) and C11;10;1 (right) from HΔ/ΔP−/− thymic lymphoma 603 (C), and the C12;15 (left) and C14;15 (right) translocations of HΔ/Δ thymic lymphoma 455 (D). SKY images are on the left, DAPI images in the middle, and computer-classified colors on the right (B–D). Cell 2003 114, 359-370DOI: (10.1016/S0092-8674(03)00566-X)

Figure 3 HΔ/ΔP−/− and H+/ΔP−/− B Lymphomas Harbor Chr 12;15 Translocations with Coamplified IgH and c-myc or IgH Fused with c-myc Exon 1 (A–E) FISH analysis with chromosome paints and locus specific probes of HΔ/ΔP−/− B cell lymphomas 888 (A and B) and 590 (C) and H+/ΔP−/− B cell lymphomas 855 (D) and 464 (E). (F) SKY analysis showing the clonal C10;12 translocation, normal chr 16, and abnormally large chr 16 of H+/ΔP−/− mature B cell lymphoma 690. The SKY image is on the left, DAPI image in the middle, and computer classified colors on the right. Cell 2003 114, 359-370DOI: (10.1016/S0092-8674(03)00566-X)

Figure 4 HΔ/ΔP−/− and H+/ΔP−/− B Lymphomas Harbor Translocations Involving IgH and c-myc Sequences (A–E) Southern blot analysis of tumor and normal kidney DNA with a JH probe (A), a 3′IgHRR probe (B), a c-myc probe (C), a Sμ probe (D), and a Jκ probe (E). The LR8 control probe was used as a control for loading (B and C) to indicate the amplification of CH and c-myc sequences. All DNAs were digested with EcoRI unless otherwise indicated. The third c-myc hybridizing band in tumor 464 (C) represents a subclonal C15;9 translocation. Cell 2003 114, 359-370DOI: (10.1016/S0092-8674(03)00566-X)

Figure 5 IgH Locus Translocation Breakpoints of HΔ/ΔP−/− and H+/ΔP−/− B Lineage Lymphomas (A) Schematic representation of where the 12;15 breakpoints (1–5) of indicated tumors map (arrows) within the IgH locus (chr 12) and c-myc (chr 15). (B) Sequences of the cloned breakpoints of the 590 and 698 complicons, an amplified junction from tumor 855, and the C12;15 translocation of tumor 464. Chr 12 sequences are in green, chr 15 sequences in red, and N nucleotides in black. Unmapped genomic sequences are indicated in lowercase black letters. Cell 2003 114, 359-370DOI: (10.1016/S0092-8674(03)00566-X)

Figure 6 H2AX Haploinsufficiency Predisposes Cells to Tumorigenesis (A and B) Western analysis of (A) H2AX expression (anti-H2AX) in H+/+P−/−, H+/ΔP−/−, and HΔ/ΔP−/− lymphomas and (B) serial 2-fold dilutions of total protein of H+/+, H+/Δ, and HΔ/Δ thymocytes. Histone H4 (anti-H4) levels control for sample loading. (C) Graph representing the average percent of H+/+, H+/Δ, and HΔ/Δ T cell metaphases with chromosomal abnormalities obtained from four independent experiments. Cell 2003 114, 359-370DOI: (10.1016/S0092-8674(03)00566-X)