PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance

M Rose, JT Burgess, K O'Byrne, DJ Richard… - Frontiers in cell and …, 2020 - frontiersin.org
The Poly (ADP-ribose) polymerase (PARP) family has many essential functions in cellular
processes, including the regulation of transcription, apoptosis and the DNA damage …

Shaping the BRCAness mutational landscape by alternative double-strand break repair, replication stress and mitotic aberrancies

C Stok, YP Kok, N van den Tempel… - Nucleic acids …, 2021 - academic.oup.com
Tumours with mutations in the BRCA1/BRCA2 genes have impaired double-stranded DNA
break repair, compromised replication fork protection and increased sensitivity to replication …

ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells

P Verma, Y Zhou, Z Cao, PV Deraska, M Deb… - Nature cell …, 2021 - nature.com
The response to poly (ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous
recombination (HR) DNA repair and the abundance of lesions that trap PARP enzymes. It …

Targeting the nucleotide salvage factor DNPH1 sensitizes BRCA-deficient cells to PARP inhibitors

K Fugger, I Bajrami, M Silva Dos Santos, SJ Young… - Science, 2021 - science.org
Mutations in the BRCA1 or BRCA2 tumor suppressor genes predispose individuals to breast
and ovarian cancer. In the clinic, these cancers are treated with inhibitors that target poly …

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 …

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 …

[HTML][HTML] PARP1: Structural insights and pharmacological targets for inhibition

JO Spiegel, B Van Houten, JD Durrant - DNA repair, 2021 - Elsevier
Abstract Poly (ADP-ribose) polymerase 1 (PARP1, also known as ADPRT1) is a
multifunctional human ADP-ribosyltransferase. It plays a role in multiple DNA repair …

To skip or not to skip: choosing repriming to tolerate DNA damage

A Quinet, S Tirman, E Cybulla, A Meroni, A Vindigni - Molecular cell, 2021 - cell.com
Accurate DNA replication is constantly threatened by DNA lesions arising from endogenous
and exogenous sources. Specialized DNA replication stress response pathways ensure …

Biochemical and structural basis for YTH domain of human YTHDC1 binding to methylated adenine in DNA

CB Woodcock, JR Horton, J Zhou… - Nucleic acids …, 2020 - academic.oup.com
The recently characterized mammalian writer (methyltransferase) and eraser (demethylase)
of the DNA N6-methyladenine (N6mA) methyl mark act on single-stranded (ss) and …