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 …
PARPi, BRCA, and gaps: controversies and future research
D Dibitetto, CA Widmer, S Rottenberg - Trends in cancer, 2024 - cell.com
In recent years, various poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) have
been approved for the treatment of several cancers to target the vulnerability of homologous …
been approved for the treatment of several cancers to target the vulnerability of homologous …
RHINO directs MMEJ to repair DNA breaks in mitosis
Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are the primary
pathways for repairing DNA double-strand breaks (DSBs) during interphase, whereas …
pathways for repairing DNA double-strand breaks (DSBs) during interphase, whereas …
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 …
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 …
Stepwise requirements for polymerases δ and θ in theta-mediated end joining
S Stroik, J Carvajal-Garcia, D Gupta, A Edwards… - Nature, 2023 - nature.com
Timely repair of chromosomal double-strand breaks is required for genome integrity and
cellular viability. The polymerase theta-mediated end joining pathway has an important role …
cellular viability. The polymerase theta-mediated end joining pathway has an important role …
Novobiocin blocks nucleic acid binding to Polθ and inhibits stimulation of its ATPase activity
A Syed, F Filandr, J Patterson-Fortin… - Nucleic acids …, 2023 - academic.oup.com
Polymerase theta (Polθ) acts in DNA replication and repair, and its inhibition is synthetic
lethal in BRCA1 and BRCA2-deficient tumor cells. Novobiocin (NVB) is a first-in-class …
lethal in BRCA1 and BRCA2-deficient tumor cells. Novobiocin (NVB) is a first-in-class …
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 …
[HTML][HTML] Spontaneous mutagenesis in human cells is controlled by REV1-Polymerase ζ and PRIMPOL
Z Gyüre, Á Póti, E Németh, B Szikriszt, R Lózsa… - Cell Reports, 2023 - cell.com
Translesion DNA synthesis (TLS) facilitates replication over damaged or difficult-to-replicate
templates by employing specialized DNA polymerases. We investigate the effect on …
templates by employing specialized DNA polymerases. We investigate the effect on …
Genetic separation of Brca1 functions reveal mutation-dependent Polθ vulnerabilities
Homologous recombination (HR)-deficiency induces a dependency on DNA polymerase
theta (Polθ/Polq)-mediated end joining, and Polθ inhibitors (Polθi) are in development for …
theta (Polθ/Polq)-mediated end joining, and Polθ inhibitors (Polθi) are in development for …