Reference

Jimeno, S., Camarillo, R., Mejías-Navarro, F., Fernández-Ávila, M.J.,Soria-Bretones, I., Prados-Carvajal, R., Huertas, P., 2018. The Helicase PIF1 Facilitates Resection over Sequences Prone to Forming G4 Structures. Cell Rep. 24 (12), 3262–3273 portada cellreports

Authors

Sonia Jimeno, Rosa Camarillo, Fernando Mejías-Navarro, María Jesús Fernández Ávila, Isabel Soria-Bretones, Rosario Prados-Carvajal, Pablo Huertas.

Abstract

DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR. The decision between these two routes of DNA repair is a key point of the DNA damage response (DDR) that is controlled by DNA resection. The core machinery catalyzing the resection process is well established. However, little is known about the additional requirements of DNA resection over DNA structures with high complexity. Here, we found evidence that the human helicase PIF1 has a role in DNA resection, specifically for defined DNA regions, such as those prone to form G-quadruplexes. Indeed, PIF1 is recruited to the site of DNA damage and physically interacts with proteins involved in DNA resection, and its depletion causes DNA damage sensitivity and a reduction of HR efficiency. Moreover, G4 stabilization by itself hampers DNA resection, a phenomenon suppressed by PIF1 overexpression.

Description

La resección del ADN es un proceso clave en la respuesta al daño celular. Sin embargo, aunque la maquinaria implicada en dicho proceso está bien caracterizada en eucariotas, aún se desconocen los factores adicionales necesarios para reseccionar a través de estructuras atípicas del ADN, como los cuádruplex de Guaninas o G-cuádruplex. En este artículo, se describe cómo la helicasa PIF1 facilita la resección a través de las secuencias del ADN que tienden a formar estas estructuras de G-cuádruplex permitiendo de este modo el acceso de la maquinaria de resección al daño.

 

 

foto PHS SEBBM

 

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo dirigido por el Dr Pablo Huertas, en el cual se ha desarrollado este trabajo, se centra en el estudio de los mecanismos implicados en la reparación del ADN y cómo afecta la correcta progresión de dichos mecanismos en diversas enfermedades, como el cáncer. Esta labor se lleva a cabo en el Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) y en la Universidad de Sevilla.

 Descargar el artículo 

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

ParB dynamics and the critical role of the CTD in DNA condensation unveiled by combined force-fluorescence measurements

01-05-2019

/Bacillus subtilis/ ParB forms multimeric networks involving non-specific DNA binding leading to DNA condensation. Previously, we found that an excess of the free C-terminal domain (CTD) of ParB impeded DNA...

Read more

Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer

01-04-2019

Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have dramatically improved the clinical outcome of HER2-positive breast cancer patients, innate and acquired resistance remains an important clinical challenge. New...

Read more

p73 regulates ependymal planar cell polarity by modulating actin and microtubule cytoskeleton

01-03-2019

Planar cell polarity (PCP) and intercellular junctional complexes establish tissue structure and coordinated behaviors across epithelial sheets. In multiciliated ependymal cells, rotational and translational PCP coordinate cilia beating and direct...

Read more

β‐RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice

01-02-2019

Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In...

Read more

Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons

02-01-2019

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of...

Read more

Dynamic acetylation of cytosolic phosphoenolpyruvate carboxykinase toggles enzyme activity between gluconeogenic and anaplerotic reactions

01-12-2018

Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts...

Read more

The Helicase PIF1 Facilitates Resection overSequences Prone to Forming G4 Structures

02-11-2018

DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR). The decision between these two routes of DNA repair is...

Read more

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

01-10-2018

The nuclear membrane acts as a mechanosensor that drives cellular responses following changes in the extracellular environment. Mechanically ventilated lungs are exposed to an abnormally high mechanical load that may...

Read more

Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

03-09-2018

Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear...

Read more

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis

01-08-2018

The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of...

Read more

Protector Members