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Structure and repair of replication-coupled DNA breaks

In this work, authored by G. Matos-Rodrigues. CRISPR-Cas9 nickases, were used to study how replication forks respond to single-strand DNA breaks.
Leading-strand nicks cause fork collapse, forming single-ended DSBs repaired via homologous recombination.
If unrepaired, neighboring forks can create double-ended DSBs, promoting genome instability in HR-deficient cells.
Lagging-strand nicks can also generate double-ended DSBs when bypassed by replication.
BRCA1 is not needed for resection here but counters 53BP1 to support RAD51 loading and fork stability.

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Re-investigating PLK1 inhibitors as antimitotic agents

Polo-like kinase 1 (PLK1) plays key roles during mitosis, prompting the development of PLK1 inhibitors for anticancer therapy. We recently determined that PLK1 is crucially required for entry into mitosis. Hence, we discuss the potential and limitations of PLK1 inhibition strategies to promote mitotic arrest and death of cancer cells.

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