Related Experiment Videos

NEK3 promotes cancer resistance through facilitating CtIP-mediated DNA repair

Yan Zhang1, Qingqiu Wen2, Haibo Huang1

  • 1Key Laboratory of Occupational Environment and Health, Guangzhou Twelfth People's Hospital 1 Tianqiang St., Huangpu West Ave., Guangzhou, Guangdong, PR China.

DNA Repair
|July 24, 2026
PubMed

Insights

Scientists found that NEK3 is crucial for repairing DNA double-strand breaks (DSBs) through homologous recombination (HR). Depleting NEK3 increases cancer cell sensitivity to radiation, suggesting new therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • DNA double-strand breaks (DSBs) represent the most severe form of DNA damage.
  • Effective repair of DSBs is essential for cellular survival and preventing cancer.
  • Protein kinases play significant roles in the complex DNA repair pathways.

Purpose of the Study:

  • To identify novel protein kinases involved in homologous recombination (HR) repair using a loss-of-function screen.
  • To investigate the role of NEK3 in DNA damage repair and its potential implications in cancer therapy.

Main Methods:

  • Utilized an optimized loss-of-function screen with a customized siRNA Premix Library.
  • Conducted experiments to assess the impact of NEK3 depletion on DNA repair and cancer cell sensitivity to ionizing radiation.

Main Results:

  • Identified NEK3 as a novel regulator essential for HR repair.
  • Demonstrated that NEK3 depletion significantly enhances the sensitivity of cancer cells to ionizing radiation.
  • Elucidated that NEK3 promotes CtIP transcription, thereby facilitating HR-mediated DNA damage repair.

Conclusions:

  • Uncovered a previously unknown function of NEK3 in DNA damage repair, specifically in HR.
  • NEK3 represents a potential therapeutic target for overcoming cancer resistance to radiotherapy and chemotherapy.
Keywords:
Cancer resistanceCtIPDNA double-strand breakHomologous recombinationKinase NEK3

Related Concept Videos

Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Nucleotide Excision Repair01:38

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...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview