Results 71 to 80 of about 76,259 (304)

Cell‐cycle‐specific lesion evolution rather than inhibition of double‐strand‐break repair underpins cisplatin radiosensitization

Molecular Oncology, EarlyView.
We analyze cisplatin–DNA adducts (CDAs) and double‐strand breaks (DSBs) in a cell‐cycle‐dependent manner. We find that CDAs form similarly across all cell cycle phases. DSBs arise only in S‐phase. CDAs might not directly impair DSB repair, but S‐phase DSB lesions evolve in the presence of CDAs and disrupt repair in G2, also causing radiosensitization ...
Ye Qiu, Xixi Lin, Emil Mladenov, Veronika Mladenova, Jürgen Thomale, Ali Sak, Yao Wang, Yunxuan Deng, Eleni Gkika, Martin Stuschke, George Iliakis   +10 more
wiley   +1 more source

RADX Modulates RAD51 Activity to Control Replication Fork Protection

Cell Reports, 2018
Summary: RAD51 promotes homologous recombination repair (HR) of double-strand breaks and acts during DNA replication to facilitate fork reversal and protect nascent DNA strands from nuclease digestion.
Kamakoti P. Bhat, Archana Krishnamoorthy, Huzefa Dungrawala, Edwige B. Garcin, Mauro Modesti, David Cortez   +5 more
doaj   +1 more source

The extent of error-prone replication-restart by homologous recombination is controlled by Exo1 and checkpoint proteins [PDF]

, 2014
Genetic instability, a hallmark of cancer, can occur when the replication machinery encounters a barrier. The intra-S phase checkpoint maintains stalled replication forks in a replication-competent configuration by phosphorylating replisome components ...
Ahn, Alabert, Bailis, Barlow, Bastia, Bester, Biswas, Boddy, Bolderson, Brown, Bähler, Carr, Carr, Casper, Cha, Chen, Cobb, Cobb, Codlin, Cotta-Ramusino, Dalgaard, De Piccoli, Durkin, El-Shemerly, Errico, Eydmann, Froget, Haghnazari, Halazonetis, Hartsuiker, Heichinger, Hu, Iraqui, Jia, Kai, Kaochar, Katou, Kolodner, Koundrioukoff, Krejci, Lambert, Lambert, Lambert, Lambert, Lambert, Lambert, Lee, Lindsay, Lisby, Lopes, Lucca, Maundrell, Meister, Mimitou, Miyabe, Miyabe, Mizuno, Mizuno, Moreau, Moreau, Moreno, Morin, Myung, Myung, Pandita, Raynard, Sabatinos, Segurado, Segurado, Smolka, Sogo, Stracker, Sun, Symington, Sørensen, Tercero, Tsubouchi, Watson, Zhu, Zou, Zubko   +80 more
core   +2 more sources

Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma

Molecular Oncology, EarlyView.
This study shows that lung adenocarcinomas exploit developmental branching morphogenesis to acquire a therapy resistant basal‐like tumour cell state. This process was found to be regulated by combined TP53 loss‐of‐function and type‐I interferon signalling, identifying a novel axis for biomarker and therapeutic target discovery.
Kamila J Bienkowska, Stephany Gallardo, Nur S. Zainal, Leena Arora, Matthew Ellis, Maria‐Antoinette Lopez, Judith Austine, Sai Pittla, Serena J Chee, Aiman Alzetani, Emily C Shaw, Christian H Ottensmeier, Gareth J Thomas, Christopher J Hanley   +13 more
wiley   +1 more source

Mutant p53 establishes targetable tumor dependency by promoting unscheduled replication [PDF]

, 2017
Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression.
Beckerman, Bronte, Catherine A. Vaughan, Frum, Lin, Luzhna, Olivier, Oren, Rebecca A. Frum, Shilpa Singh, Steven R. Grossman, Sumitra Deb, Swati Palit Deb, Zeman, Zuazua-Villar   +14 more
core   +2 more sources

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

Molecular Oncology, EarlyView.
Synthetic lethality screens performed to identify novel vulnerabilities often model complete gene loss, thereby overlooking patient‐derived hypomorphic mutations. In this study, we have performed genome‐wide CRISPR screens on BRCA1 hypomorphic mutations, showing BRCA1I26A behaves like wild‐type, while BRCA1R1699Q mimics deficiency. Furthermore, we have
Anne Schreuder, Klaas de Lint, Hồ Mỹ Phúc Võ, Mariana M. Góis, Rosalie A. Kampen, Marta San Martin Alonso, Ilse Nootenboom, Veronica Garzero, Tiemen J. Wendel, Rob M. F. Wolthuis, Sylvie M. Noordermeer   +10 more
wiley   +1 more source

Rad53-Mediated Regulation of Rrm3 and Pif1 DNA Helicases Contributes to Prevention of Aberrant Fork Transitions under Replication Stress

Cell Reports, 2015
Replication stress activates the Mec1ATR and Rad53 kinases. Rad53 phosphorylates nuclear pores to counteract gene gating, thus preventing aberrant transitions at forks approaching transcribed genes.
Silvia Emma Rossi, Arta Ajazi, Walter Carotenuto, Marco Foiani, Michele Giannattasio   +4 more
doaj   +1 more source

FANCD2 maintains replication fork stability during misincorporation of the DNA demethylation products 5-hydroxymethyl-2’-deoxycytidine and 5-hydroxymethyl-2’-deoxyuridine

Cell Death and Disease, 2022
Fanconi anemia (FA) is a rare hereditary disorder caused by mutations in any one of the FANC genes. FA cells are mainly characterized by extreme hypersensitivity to interstrand crosslink (ICL) agents.
María José Peña-Gómez, Paula Moreno-Gordillo, Milda Narmontė, Clara B. García-Calderón, Audronė Rukšėnaitė, Saulius Klimašauskas, Iván V. Rosado   +6 more
doaj   +1 more source

RTEL1 and MCM10 overcome topological stress during vertebrate replication termination

Cell Reports, 2023
Summary: Topological stress can cause converging replication forks to stall during termination of vertebrate DNA synthesis. However, replication forks ultimately overcome fork stalling, suggesting that alternative mechanisms of termination exist.
Lillian V. Campos, Sabrina X. Van Ravenstein, Emma J. Vontalge, Briana H. Greer, Darren R. Heintzman, Tamar Kavlashvili, W. Hayes McDonald, Kristie Lindsey Rose, Brandt F. Eichman, James M. Dewar   +9 more
doaj   +1 more source

The causes and consequences of topological stress during DNA replication [PDF]

, 2016
The faithful replication of sister chromatids is essential for genomic integrity in every cell division. The replication machinery must overcome numerous difficulties in every round of replication, including DNA topological stress.
Andrea Keszthelyi, Champoux, Hiasa, Hiasa, Hiasa, Jonathan Baxter, Kornberg, Nicola Minchell   +7 more
core   +2 more sources