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Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
TLDR
It is proposed that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair and exploited in order to kill BRCA2-deficient tumours by PARP inhibition alone.
DNA repair pathways as targets for cancer therapy
TLDR
There is evidence that drugs that inhibit one of these pathways in such tumours could prove useful as single-agent therapies, with the potential advantage that this approach could be selective for tumour cells and have fewer side effects.
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
TLDR
It is shown that oncogene-induced senescence is associated with signs of DNA replication stress, including prematurely terminated DNA replication forks and DNA double-strand breaks, and, together with apoptosis, provides a barrier to malignant progression.
The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair
TLDR
It is established that Chk1 is a key regulator of genome maintenance by the homologous recombination repair (HRR) system, and that RAD51 is phosphorylated on Thr 309 in a ChK1-dependent manner, highlighting a crucial role for the Chk2 signalling pathway in protecting cells against lethal DNA lesions through regulation of HRR.
Inhibition of Human Chk1 Causes Increased Initiation of DNA Replication, Phosphorylation of ATR Targets, and DNA Breakage
TLDR
It is proposed that Chk1 is required during normal S phase to avoid aberrantly increased initiation of DNA replication, thereby protecting against DNA breakage.
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
TLDR
This corrects the article to show that the method used to derive the H2O2 “spatially aggregating force” is based on a two-step process, not a single step, like in the previous version of this paper.
PARP is activated at stalled forks to mediate Mre11‐dependent replication restart and recombination
TLDR
Together, the data suggest that PARP1 and PARP2 detect disrupted replication forks and attract Mre11 for end processing that is required for subsequent recombination repair and restart of replication forks.
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