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Domenic Pilger

As seen in: Nature, BioRxiv
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Articles

USP37 prevents premature disassembly of stressed replisomes by TRAIP - Nature Communications

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By Giuseppina D’Alessandro, Domenic Pilger, Ernst W. Schmid, Satpal S Jhujh, Christopher J. Carnie, Simon Lam, Grant Stewart, Johannes C. Walter
| Nature Verified
Abstract The eukaryotic replisome, which consists of the CDC45-MCM2-7-GINS (CMG) helicase, replicative polymerases, and several accessory factors, sometimes encounters proteinaceous obstacles that threaten genome integrity. These obstacles are targeted for removal or proteolysis by the E3 ubiquitin ligase TRAIP, which associates with the replisome. However, TRAIP must be carefully regulated to avoid inappropriate ubiquitylation and disassembly of the replisome.
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Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial - Nature Communications

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By Jean Abraham, Karen Pinilla Alba, Rebecca Lucey, Anita Chhabra, Wendi Qian, Domenic Pilger, Rebecca Roylance, Anne Armstrong, Marc Tischkowitz, Mark O’Connor, Lenka Oplustil O’Connor
| Nature Verified
Abstract Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity.
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USP37 prevents premature disassembly of stressed replisomes by TRAIP

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By Olga V. Kochenova, Giuseppina D'Alessandro, Domenic Pilger, Ernst W. Schmid
| BioRxiv
Abstract The E3 ubiquitin ligase TRAIP associates with the replisome and helps this molecular machine deal with replication stress. Thus, TRAIP promotes DNA inter-strand crosslink repair by triggering the disassembly of CDC45-MCM2-7-GINS (CMG) helicases that have converged on these lesions. However, disassembly of single CMGs that have stalled temporarily would be deleterious, suggesting that TRAIP must be carefully regulated.
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