Video Experimental Relacionado

Updated: Nov 9, 2025

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

Dirigirse al factor de rescate de nucleótidos DNPH1 sensibiliza a las células con deficiencia de BRCA a los

Kasper Fugger¹, Ilirjana Bajrami², Mariana Silva Dos Santos²

¹The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. stephen.west@crick.ac.uk kasper.fugger@crick.ac.uk.

Science (New York, N.Y.)

|April 9, 2021

Resumen

La orientación a DNPH1 mejora el tratamiento del cáncer en pacientes con deficiencia de BRCA. La inhibición de DNPH1 aumenta la sensibilidad a los inhibidores de PARP (PARPi) al aumentar los niveles de nucleótidos citotóxicos, lo que lleva a la muerte de las células cancerosas.

Área de la Ciencia:

Genética y genómica
Biología del cáncer
Descubrimiento de drogas

Sus antecedentes:

Las mutaciones BRCA1/BRCA2 aumentan el riesgo de cáncer de mama y de ovario.
Los inhibidores de la poli (ADP-ribosa) polimerasa (PARPi) se utilizan para el tratamiento de estos cánceres.

Objetivo del estudio:

Investigar si la inhibición de DNPH1 puede mejorar la eficacia de PARPi en cánceres con deficiencia de BRCA.
Explorar el mecanismo de letalidad sintética inducida por la inhibición de DNPH1 y PARPi.

Principales métodos:

Utilizando modelos de cultivo celular de cánceres con deficiencia de BRCA.
Utilizando la inhibición de DNPH1 y el tratamiento con 5-hidroximetildeoxyuridina (hmdU).
Evaluación de la sensibilidad a los inhibidores de la PARP (PARPi) y análisis de las vías de respuesta al daño del ADN.

Principales resultados:

La inhibición de DNPH1 potencia la sensibilidad PARPi en las células con deficiencia de BRCA.
La acumulación genómica de hmdU desencadena la letalidad sintética a través de la captura de PARP y el colapso de la bifurcación de replicación.
La inhibición de DNPH1 vuelve a sensibilizar las células resistentes al PARPi.

Conclusiones:

La inhibición de DNPH1 es una estrategia prometedora para potenciar la terapia PARPi en cánceres con deficiencia de BRCA.
Dirigirse a DNPH1 ofrece un nuevo enfoque para superar la resistencia a PARPi.

Más Videos Relacionados

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair

gDNA Enrichment by a Transposase-based Technology for NGS Analysis of the Whole Sequence of BRCA1, BRCA2, and 9 Genes Involved in DNA Damage Repair

Published on: October 6, 2014

Videos de Conceptos Relacionados

DNA Damage can Stall the Cell Cycle

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Long-patch Base Excision Repair

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:

Base Excision Repair

Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...

Restarting Stalled Replication Forks

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...

Nucleotide Excision Repair

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...