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Article
Open AccessA HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant
Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previ...
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Article
Open AccessFunctional screening reveals HORMAD1-driven gene dependencies associated with translesion synthesis and replication stress tolerance
HORMAD1 expression is usually restricted to germline cells, but it becomes mis-expressed in epithelial cells in ~60% of triple-negative breast cancers (TNBCs), where it is associated with elevated genomic inst...
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Article
Open AccessAuthor Correction: Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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Article
The shieldin complex mediates 53BP1-dependent DNA repair
53BP1 is a chromatin-binding protein that regulates the repair of DNA double-strand breaks by suppressing the nucleolytic resection of DNA termini1,2. This function of 53BP1 requires interactions with PTIP3 and R...
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Article
Open AccessChemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness
Osteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygo...
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Article
Open AccessGenome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance
Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-C...
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Article
Open AccessGenome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells
We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximatel...
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Article
Open AccessMolecular characterisation of cell line models for triple-negative breast cancers
Triple-negative breast cancers (BC) represent a heterogeneous subtype of BCs, generally associated with an aggressive clinical course and where targeted therapies are currently limited. Target validation studi...
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Article
Open AccessHigh-throughput RNA interference screening using pooled shRNA libraries and next generation sequencing
RNA interference (RNAi) screening is a state-of-the-art technology that enables the dissection of biological processes and disease-related phenotypes. The commercial availability of genome-wide, short hairpin ...