Related Experiment Video

Updated: May 29, 2026

Dual Immunofluorescence of γH2AX and 53BP1 in Human Peripheral Lymphocytes
05:34

Dual Immunofluorescence of γH2AX and 53BP1 in Human Peripheral Lymphocytes

Published on: July 14, 2023

ASPM influences DNA double-strand break repair and represents a potential target for radiotherapy

Takamitsu A Kato1, Ryuichi Okayasu, Penny A Jeggo

  • 1Heavy-Ion Radiobiology Research Group, Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba, Japan.

International Journal of Radiation Biology
|September 20, 2011
PubMed
Abstract

Insights

Abnormal spindle-like microcephaly-associated (ASPM) gene reduction enhances radiosensitivity by impairing DNA repair. ASPM is crucial for DNA double-strand break repair and may be a therapeutic target for radiation combination therapy.

Area of Science:

  • Molecular Biology
  • Genetics
  • Radiation Oncology

Background:

  • ASPM (abnormal spindle-like microcephaly-associated) is implicated in microcephaly (MCPH5).
  • Previous studies showed Ionizing Radiation (IR) down-regulates ASPM.
  • The role of ASPM in radiosensitivity was previously uninvestigated.

Purpose of the Study:

  • To investigate the role of ASPM in cellular response to IR.
  • To determine if ASPM affects radiosensitivity, DNA repair, and chromosome stability.

Main Methods:

  • Used glioblastoma cell lines and normal human fibroblasts.
  • Reduced ASPM expression using small interfering RNA (siRNA).
  • Assessed IR sensitivity via survived fraction, DNA double-strand break (DSB) repair (γ-H2AX foci), and chromosome aberration analysis.

Main Results:

  • ASPM down-regulation by siRNA significantly enhanced radiosensitivity in all tested human cell lines.
  • ASPM knockdown impaired DNA double-strand break (DSB) repair following IR.
  • Elevated chromosome aberrations and impaired DNA repair suggest ASPM's role in non-homologous end-joining (NHEJ).
  • IR-sensitization was not enhanced in DNA-PK deficient cells, indicating a DNA-PK-dependent pathway.

Conclusions:

  • ASPM is essential for efficient non-homologous end-joining (NHEJ) DNA repair in mammalian cells.
  • ASPM represents a potential novel therapeutic target for combination therapy with radiation.
  • ASPM may serve as a valuable biomarker for predicting tumor prognosis in clinical settings.

More Related Videos

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells05:18

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

Immunofluorescence Microscopy of γH2AX and 53BP1 for Analyzing the Formation and Repair of DNA Double-strand Breaks10:47

Immunofluorescence Microscopy of γH2AX and 53BP1 for Analyzing the Formation and Repair of DNA Double-strand Breaks

Published on: November 3, 2017

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

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...
DNA Damage Can Stall the Cell Cycle02:36

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...
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
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...