Targeting replication stress in cancer therapy
AABA da Costa, D Chowdhury, GI Shapiro… - Nature reviews Drug …, 2023 - nature.com
Replication stress is a major cause of genomic instability and a crucial vulnerability of
cancer cells. This vulnerability can be therapeutically targeted by inhibiting kinases that …
cancer cells. This vulnerability can be therapeutically targeted by inhibiting kinases that …
Leveraging the replication stress response to optimize cancer therapy
E Cybulla, A Vindigni - Nature Reviews Cancer, 2023 - nature.com
High-fidelity DNA replication is critical for the faithful transmission of genetic information to
daughter cells. Following genotoxic stress, specialized DNA damage tolerance pathways …
daughter cells. Following genotoxic stress, specialized DNA damage tolerance pathways …
Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency
Mutations in BRCA1 or BRCA2 (BRCA) is synthetic lethal with poly (ADP-ribose)
polymerase inhibitors (PARPi). Lethality is thought to derive from DNA double-stranded …
polymerase inhibitors (PARPi). Lethality is thought to derive from DNA double-stranded …
Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells
PRIMPOL repriming allows DNA replication to skip DNA lesions, leading to ssDNA gaps.
These gaps must be filled to preserve genome stability. Using a DNA fiber approach to …
These gaps must be filled to preserve genome stability. Using a DNA fiber approach to …
REV1-Polζ maintains the viability of homologous recombination-deficient cancer cells through mutagenic repair of PRIMPOL-dependent ssDNA gaps
BRCA1/2 mutant tumor cells display an elevated mutation burden, the etiology of which
remains unclear. Here, we report that these cells accumulate ssDNA gaps and spontaneous …
remains unclear. Here, we report that these cells accumulate ssDNA gaps and spontaneous …
[HTML][HTML] POLθ processes ssDNA gaps and promotes replication fork progression in BRCA1-deficient cells
A Schrempf, S Bernardo, EAA Verge, MAR Otero… - Cell reports, 2022 - cell.com
Polymerase theta (POLθ) is an error-prone DNA polymerase whose loss is synthetically
lethal in cancer cells bearing breast cancer susceptibility proteins 1 and 2 (BRCA1/2) …
lethal in cancer cells bearing breast cancer susceptibility proteins 1 and 2 (BRCA1/2) …
Mitotic DNA synthesis in response to replication stress requires the sequential action of DNA polymerases zeta and delta in human cells
W Wu, SA Barwacz, R Bhowmick, K Lundgaard… - Nature …, 2023 - nature.com
Oncogene activation creates DNA replication stress (RS) in cancer cells, which can
generate under-replicated DNA regions (UDRs) that persist until cells enter mitosis. UDRs …
generate under-replicated DNA regions (UDRs) that persist until cells enter mitosis. UDRs …
Replication gaps underlie BRCA deficiency and therapy response
NJ Panzarino, JJ Krais, K Cong, M Peng, M Mosqueda… - Cancer research, 2021 - AACR
Defects in DNA repair and the protection of stalled DNA replication forks are thought to
underlie the chemosensitivity of tumors deficient in the hereditary breast cancer genes …
underlie the chemosensitivity of tumors deficient in the hereditary breast cancer genes …
The trans cell cycle effects of PARP inhibitors underlie their selectivity toward BRCA1/2-deficient cells
A Simoneau, R Xiong, L Zou - Genes & Development, 2021 - genesdev.cshlp.org
PARP inhibitor (PARPi) is widely used to treat BRCA1/2-deficient tumors, but why PARPi is
more effective than other DNA-damaging drugs is unclear. Here, we show that PARPi …
more effective than other DNA-damaging drugs is unclear. Here, we show that PARPi …
APOBEC3A induces DNA gaps through PRIMPOL and confers gap-associated therapeutic vulnerability
Mutation signatures associated with apolipoprotein B mRNA editing catalytic polypeptide-
like 3A/B (APOBEC3A/B) cytidine deaminases are prevalent across cancers, implying their …
like 3A/B (APOBEC3A/B) cytidine deaminases are prevalent across cancers, implying their …