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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 …
BRCAness, DNA gaps, and gain and loss of PARP inhibitor–induced synthetic lethality
Mutations in the tumor-suppressor genes BRCA1 and BRCA2 resulting in BRCA1/2
deficiency are frequently identified in breast, ovarian, prostate, pancreatic, and other …
deficiency are frequently identified in breast, ovarian, prostate, pancreatic, and other …
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 …
[HTML][HTML] Exploiting replication gaps for cancer therapy
Defects in DNA double-strand break repair are thought to render BRCA1 or BRCA2 (BRCA)
mutant tumors selectively sensitive to PARP inhibitors (PARPis). Challenging this …
mutant tumors selectively sensitive to PARP inhibitors (PARPis). Challenging this …
[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) …
EXO1 protects BRCA1-deficient cells against toxic DNA lesions
B van de Kooij, A Schreuder, R Pavani, V Garzero… - Molecular Cell, 2024 - cell.com
Inactivating mutations in the BRCA1 and BRCA2 genes impair DNA double-strand break
(DSB) repair by homologous recombination (HR), leading to chromosomal instability and …
(DSB) repair by homologous recombination (HR), leading to chromosomal instability and …
Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy
DNA damage tolerance and mutagenesis are hallmarks and enabling characteristics of
neoplastic cells that drive tumorigenesis and allow cancer cells to resist therapy. The 'Y …
neoplastic cells that drive tumorigenesis and allow cancer cells to resist therapy. The 'Y …
ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms
The ATR kinase safeguards genomic integrity during S phase, but how ATR protects DNA
replication forks remains incompletely understood. Here, we combine four distinct assays to …
replication forks remains incompletely understood. Here, we combine four distinct assays to …
Multi-step processing of replication stress-derived nascent strand DNA gaps by MRE11 and EXO1 nucleases
A Hale, A Dhoonmoon, J Straka, CM Nicolae… - Nature …, 2023 - nature.com
Accumulation of single stranded DNA (ssDNA) gaps in the nascent strand during DNA
replication has been associated with cytotoxicity and hypersensitivity to genotoxic stress …
replication has been associated with cytotoxicity and hypersensitivity to genotoxic stress …
[HTML][HTML] Mechanism of PARP inhibitor resistance and potential overcoming strategies
PARP inhibitors (PARPi) are a kind of cancer therapy that targets poly (ADP-ribose)
polymerase. PARPi is the first clinically approved drug to exert synthetic lethality by …
polymerase. PARPi is the first clinically approved drug to exert synthetic lethality by …