The telomeric DNA damage response occurs in the absence of chromatin decompaction

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A Role for Human DNA Polymerase λ in Alternative Lengthening of Telomeres

Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addi ...

2021

RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops

Joachim Lingner, Thomas Frédéric Lunardi, Marianna Feretzaki, Rita Valador Fernandes

Telomeres-repeated, noncoding nucleotide motifs and associated proteins that are found at the ends of eukaryotic chromosomes-mediate genome stability and determine cellular lifespan1. Telomeric-repeat-containing RNA (TERRA) is a class of long noncoding RNA ...

2020

PRDX1 Counteracts Catastrophic Telomeric Cleavage Events That Are Triggered by DNA Repair Activities Post Oxidative Damage

Joachim Lingner, Wareed Ahmed

Telomeres are prone to damage inflicted by reactive oxygen species (ROS). Oxidized telomeric DNA and nucleotide substrates inhibit telomerase, causing telomere shortening. In addition, ROS can induce telomeric single-strand DNA breaks (SSBs). The peroxired ...

2020

SMCHD1 promotes ATM-dependent DNA damage signaling and repair of uncapped telomeres

Joachim Lingner, Wareed Ahmed, Verena Pfeiffer, Marianna Feretzaki, Aleksandra Vancevska

Structural maintenance of chromosomes flexible hinge domain-containing protein 1 (SMCHD1) has been implicated in X-chromosome inactivation, imprinting, and DNA damage repair, and mutations in SMCHD1 can cause facioscapulohumeral muscular dystrophy. More re ...

WILEY2020

Requirements for DNA bubble structure for efficient cleavage by helix-two-turn-helix DNA glycosylases

Kristina Makasheva

Oxidative DNA lesions, constantly generated by both endogenous and environmentally induced reactive oxygen species, are removed via the base excision repair pathway. In bacteria, Fpg and Nei DNA glycosylases, belonging to the helix-two-turn-helix (H2TH) st ...

2020

Genome-wide Screens Implicate Loss of Cullin Ring Ligase 3 in Persistent Proliferation and Genome Instability in TP53-Deficient Cells

Sebastian Martin Waszak, Ruxandra-Andreea Lambuta

TP53 deficiency is the most common alteration in cancer; however, this alone is typically insufficient to drive tumorigenesis. To identify genes promoting tumorigenesis in combination with TP53 deficiency, we perform genome-wide CRISPR-Cas9 knockout screen ...

2020

Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and vascular senescence

Johan Auwerx, Norman Lionel Moullan, Lei Chen

Long noncoding RNAs (lncRNAs) are emerging regulators of biological processes in the vessel wall; however, their role in atherosclerosis remains poorly defined. We used RNA sequencing to profile lncRNAs derived specifically from the aortic intima of Ldlr(- ...

AMER ASSOC ADVANCEMENT SCIENCE2020

Structural transitions and mechanochemical coupling in the nucleoprotein filament explain homology selectivity and Rad51 protein cooperativity in cellular DNA repair

Daniel Migliozzi

The nucleoprotein filament (NPF) is the fundamental element of homologous recombination (HR), a major mechanism for the repair of double-strand DNA breaks in the cell. The NPF is made of the damaged DNA strand surrounded by recombinase proteins, and its se ...

AMER PHYSICAL SOC2020

A scalable CRISPR/Cas9-based fluorescent reporter assay to study DNA double-strand break repair choice

Stephanie Jocelyne Sungalee

Double-strand breaks (DSBs) are the most toxic type of DNA lesions. Cells repair these lesions using either end protection- or end resection-coupled mechanisms. To study DSB repair choice, we present the Color Assay Tracing-Repair (CAT-R) to simultaneously ...

Nature Research2020

RADX: A novel single-stranded DNA-binding protein regulating telomere recombination

Anna-Sophia Briod

Telomeres are specialized nucleoprotein structures present at the ends of linear chromosome. The telomeric DNA part is comprised of 5-15 kilo base pairs of double stranded TTAGGG repeats and it contains at the 3' end a single-stranded G-rich overhang of 50 ...

EPFL2019

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