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XB-ART-51880
J Cell Biol February 15, 2016; 212 (4): 399-408.

MRN, CtIP, and BRCA1 mediate repair of topoisomerase II-DNA adducts.

Aparicio T , Baer R , Gottesman M , Gautier J .


Abstract
Repair of DNA double-strand breaks (DSBs) with complex ends poses a special challenge, as additional processing is required before DNA ligation. For example, protein-DNA adducts must be removed to allow repair by either nonhomologous end joining or homology-directed repair. Here, we investigated the processing of topoisomerase II (Top2)-DNA adducts induced by treatment with the chemotherapeutic agent etoposide. Through biochemical analysis in Xenopus laevis egg extracts, we establish that the MRN (Mre11, Rad50, and Nbs1) complex, CtIP, and BRCA1 are required for both the removal of Top2-DNA adducts and the subsequent resection of Top2-adducted DSB ends. Moreover, the interaction between CtIP and BRCA1, although dispensable for resection of endonuclease-generated DSB ends, is required for resection of Top2-adducted DSBs, as well as for cellular resistance to etoposide during genomic DNA replication.

PubMed ID: 26880199
PMC ID: PMC4754713
Article link: J Cell Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: brca1 gnl3 rad50 rbbp8 top2a


Article Images: [+] show captions
References [+] :
Andres, Recognition and repair of chemically heterogeneous structures at DNA ends. 2015, Pubmed