[HTML][HTML] Exploiting replication gaps for cancer therapy

K Cong, SB Cantor - Molecular cell, 2022 - cell.com
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 …

Advances in understanding DNA processing and protection at stalled replication forks

K Rickman, A Smogorzewska - Journal of Cell Biology, 2019 - rupress.org
The replisome, the molecular machine dedicated to copying DNA, encounters a variety of
obstacles during S phase. Without a proper response to this replication stress, the genome …

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 …

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 …

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 …

Inhibition of the translesion synthesis polymerase REV1 exploits replication gaps as a cancer vulnerability

S Nayak, JA Calvo, K Cong, M Peng, E Berthiaume… - Science …, 2020 - science.org
The replication stress response, which serves as an anticancer barrier, is activated not only
by DNA damage and replication obstacles but also oncogenes, thus obscuring how cancer …

How do mutations affecting the breast cancer genes BRCA1 and BRCA2 cause cancer susceptibility?

AR Venkitaraman - DNA repair, 2019 - Elsevier
The inheritance of monoallelic germline mutations affecting BRCA1 or BRCA2 predisposes
with a high penetrance to several forms of epithelial malignancy. The large, nuclear …

History of DNA helicases

RM Brosh Jr, SW Matson - Genes, 2020 - mdpi.com
Since the discovery of the DNA double helix, there has been a fascination in understanding
the molecular mechanisms and cellular processes that account for:(i) the transmission of …

The emerging determinants of replication fork stability

T Thakar, GL Moldovan - Nucleic acids research, 2021 - academic.oup.com
A universal response to replication stress is replication fork reversal, where the nascent
complementary DNA strands are annealed to form a protective four-way junction allowing …

Loss of nuclear DNA ligase III reverts PARP inhibitor resistance in BRCA1/53BP1 double-deficient cells by exposing ssDNA gaps

MP Dias, V Tripathi, I van der Heijden, K Cong… - Molecular cell, 2021 - cell.com
Inhibitors of poly (ADP-ribose)(PAR) polymerase (PARPi) have entered the clinic for the
treatment of homologous recombination (HR)-deficient cancers. Despite the success of this …