The plasticity of DNA replication forks in response to clinically relevant genotoxic stress

M Berti, D Cortez, M Lopes - Nature reviews Molecular cell biology, 2020 - nature.com
Complete and accurate DNA replication requires the progression of replication forks through
DNA damage, actively transcribed regions, structured DNA and compact chromatin. Recent …

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 …

Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency

K Cong, M Peng, AN Kousholt, WTC Lee, S Lee… - Molecular cell, 2021 - cell.com
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 …

Structure and repair of replication-coupled DNA breaks

R Pavani, V Tripathi, KB Vrtis, D Zong, R Chari… - Science, 2024 - science.org
Using CRISPR-Cas9 nicking enzymes, we examined the interaction between the replication
machinery and single-strand breaks, one of the most common forms of endogenous DNA …

Temporally distinct post-replicative repair mechanisms fill PRIMPOL-dependent ssDNA gaps in human cells

S Tirman, A Quinet, M Wood, A Meroni, E Cybulla… - Molecular cell, 2021 - cell.com
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 …

REV1-Polζ maintains the viability of homologous recombination-deficient cancer cells through mutagenic repair of PRIMPOL-dependent ssDNA gaps

A Taglialatela, G Leuzzi, V Sannino, R Cuella-Martin… - Molecular cell, 2021 - cell.com
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 …

RAD51 bypasses the CMG helicase to promote replication fork reversal

W Liu, Y Saito, J Jackson, R Bhowmick, MT Kanemaki… - Science, 2023 - science.org
Replication fork reversal safeguards genome integrity as a replication stress response. DNA
translocases and the RAD51 recombinase catalyze reversal. However, it remains unknown …

[HTML][HTML] BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair

PX Lim, M Zaman, W Feng, M Jasin - Molecular cell, 2024 - cell.com
Tumor suppressor BRCA2 functions in homology-directed repair (HDR), the protection of
stalled replication forks, and the suppression of replicative gaps, but their relative …

Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability

V Gaggioli, CSY Lo, N Reverón-Gómez… - Nature cell …, 2023 - nature.com
Chromatin is dynamically reorganized when DNA replication forks are challenged. However,
the process of epigenetic reorganization and its implication for fork stability is poorly …

HLTF promotes fork reversal, limiting replication stress resistance and preventing multiple mechanisms of unrestrained DNA synthesis

G Bai, C Kermi, H Stoy, CJ Schiltz, J Bacal, AM Zaino… - Molecular cell, 2020 - cell.com
DNA replication stress can stall replication forks, leading to genome instability. DNA damage
tolerance pathways assist fork progression, promoting replication fork reversal, translesion …