Fig. 7: TOP2B is enriched at V(D)J-active regions colocalizing with RAG and endogenous DSB accumulation. | Nature Communications

Fig. 7: TOP2B is enriched at V(D)J-active regions colocalizing with RAG and endogenous DSB accumulation.

From: Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

Fig. 7

a–c Genome browser view of TOP2B, RAD21, RAG1, RAG2 and ENDseq signal tracks in wild-type, Atm−/− and Rag2−/− primary thymocytes, as indicated, at IgH (a), Tcra/d (b) and Tcrb (c) loci. TOP2B enriched regions are highlighted in grey. Regions of V, D or J segments are indicated. ENDseq signal in Rag2−/− thymocytes is additionally shown with a smaller scale to appreciate sites of minor DSB accumulation (yellow, auto). d, e Endogenous accumulation of TOP2Bccs and TOP2-mediated DSBs, as measured with ICE-IP, at Tcrb (d) and Pten (e) loci in Tdp2+/+ Atm+/+, Tdp2−/− Atm+/+, Tdp2+/+ Atm−/− and Tdp2−/− Atm−/− freshly isolated thymocytes from three independent mice (n = 3). Regions 1 and 2 for Tcrb and Pten are indicated in Fig. 7c and 5c, respectively. Mean ± SEM and statistical significance by one-way ANOVA (non-parametric) with Dunn’s post-test is shown (F = 9 for region 1 of Pten and F = 5,8 and F = 7 for region 1 and region 2 of Tcrb).

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