Replication fork reversal triggers fork degradation in BRCA2-defective cells

Mijic, Sofija; Zellweger, Ralph; Chappidi, Nagaraja; Berti, Matteo; Jacobs, Kurt; Mutreja, Karun; Ursich, Sebastian; Ray Chaudhuri, Arnab; Nussenzweig, Andre; Janscak, Pavel; Lopes, Massimo

doi:10.1038/s41467-017-01164-5

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Mijic, S., Zellweger, R., Chappidi, N., Berti, M., Jacobs, K., Mutreja, K., Ursich, S., Ray Chaudhuri, A., Nussenzweig, A., Janscak, P., & Lopes, M. (2017). Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nature Communications, 8, 859. https://doi.org/10.1038/s41467-017-01164-5

Abstract

Besides its role in homologous recombination, the tumor suppressor BRCA2 protects stalled replication forks from nucleolytic degradation. Defective fork stability contributes to chemotherapeutic sensitivity of BRCA2-defective tumors by yet-elusive mechanisms. Using DNA fiber spreading and direct visualization of replication intermediates, we report that reversed replication forks are entry points for fork degradation in BRCA2-defective cells. Besides MRE11 and PTIP, we show that RAD52 promotes stalled fork degradation and chromosomal