American Society of Hematology

Figure 3.

$Figure 3. Rev1 protects against replication stress and genomic breaks in the hematopoietic system (see also supplemental Figure 4). We investigated the induction of DNA breaks in the absence of Rev1-mediated TLS at endogenous helix-distorting DNA lesions in blood and bone marrow. *P < .05; **P < .01; ***P < .001; ****P < .0001. Data are mean ± SEM. (A) Chromosome fragments (Howell-Jolly bodies, arrowheads) in erythrocytes of 3-month-old Rev1 and Rev1Xpc mice. Bar represents 10 μm. Right panel: quantification. WT: 3 m (n = 5), MB (n = 6). Xpc: 3 m (n = 5), MB (n = 6). Rev1: 3 m (n = 5), MB (n = 9). Rev1Xpc: 3 m (n = 6), MB (n = 8). (B) Chromosome breaks outside of S phase, measured by single-cell alkaline comet gel electrophoresis of bone marrow of 3-month-old mice. WT (n = 4), Xpc (n = 4), Rev1 (n = 4), Rev1Xpc (n = 4). Comet intensities of BrdU-negative cells are shown. Increased DNA breaks in bone marrow hematopoietic cells of Rev1 and Rev1Xpc mice as demonstrated by γH2AX (C) and 53BP1 (D) immunostaining. The fraction of positive cells shown was normalized relative to 3-month-old WT. WT: 3 m (n = 8), MB (n = 6). Xpc: 3 m (n = 7), MB (n = 6). Rev1: 3 m (n = 6), MB (n = 6). Rev1Xpc: 3 m (n = 5-6), MB (n = 9).$

Rev1 protects against replication stress and genomic breaks in the hematopoietic system (see alsosupplemental Figure 4). We investigated the induction of DNA breaks in the absence of Rev1-mediated TLS at endogenous helix-distorting DNA lesions in blood and bone marrow. *P < .05; **P < .01; ***P < .001; ****P < .0001. Data are mean ± SEM. (A) Chromosome fragments (Howell-Jolly bodies, arrowheads) in erythrocytes of 3-month-old Rev1 and Rev1Xpc mice. Bar represents 10 μm. Right panel: quantification. WT: 3 m (n = 5), MB (n = 6). Xpc: 3 m (n = 5), MB (n = 6). Rev1: 3 m (n = 5), MB (n = 9). Rev1Xpc: 3 m (n = 6), MB (n = 8). (B) Chromosome breaks outside of S phase, measured by single-cell alkaline comet gel electrophoresis of bone marrow of 3-month-old mice. WT (n = 4), Xpc (n = 4), Rev1 (n = 4), Rev1Xpc (n = 4). Comet intensities of BrdU-negative cells are shown. Increased DNA breaks in bone marrow hematopoietic cells of Rev1 and Rev1Xpc mice as demonstrated by γH2AX (C) and 53BP1 (D) immunostaining. The fraction of positive cells shown was normalized relative to 3-month-old WT. WT: 3 m (n = 8), MB (n = 6). Xpc: 3 m (n = 7), MB (n = 6). Rev1: 3 m (n = 6), MB (n = 6). Rev1Xpc: 3 m (n = 5-6), MB (n = 9).

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