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Updated: Dec 29, 2025

Author Spotlight: Characterizing DNA Replication of Pathogenic Repeats to Uncover Mechanisms of Replication Fork Stalling and Expansion
Published on: September 13, 2024
BLM has Contrary Effects on Repeat-Mediated Deletions, based on the Distance of DNA DSBs to a Repeat and Repeat
Carlos Mendez-Dorantes1, L Jillianne Tsai1, Eva Jahanshir2
1Department of Cancer Genetics and Epigenetics, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Abstract:
Repeat-mediated deletions (RMDs) often involve repetitive elements (e.g., short interspersed elements) with sequence divergence that is separated by several kilobase pairs (kbps). We have examined RMDs induced by DNA double-strand breaks (DSBs) under varying conditions of repeat sequence divergence (identical versus 1% and 3% divergent) and DSB/repeat distance (16 bp-28.4 kbp). We find that the BLM helicase promotes RMDs with long DSB/repeat distances (e.g., 28.4 kbp), which is consistent with a role in extensive DSB end resection, because the resection nucleases EXO1 and DNA2 affect RMDs similarly to BLM. In contrast, BLM suppresses RMDs with sequence divergence and intermediate (e.g., 3.3 kbp) DSB/repeat distances, which supports a role in heteroduplex rejection. The role of BLM in heteroduplex rejection is not epistatic with MSH2 and is independent of the annealing factor RAD52. Accordingly, the role of BLM on RMDs is substantially affected by DSB/repeat distance and repeat sequence divergence.
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