Related Experiment Video

Updated: Apr 21, 2026

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
05:18

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

Published on: June 9, 2020

10.9K

The RASSF1A tumor suppressor regulates XPA-mediated DNA repair

Howard Donninger1, Jennifer Clark1, Francesca Rinaldo1

  • 1Department of Medicine, J. G. Brown Cancer Center, Molecular Targets Program, University of Louisville, Louisville, Kentucky, USA.

Molecular and Cellular Biology
|November 5, 2014
PubMed

Insights

The tumor suppressor RASSF1A is crucial for DNA repair and the apoptotic DNA damage response (DDR). It interacts with XPA, and its deficiency impairs DNA repair, with a cancer SNP variant hindering this process.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The tumor suppressor RASSF1A is frequently inactivated in human cancers.
  • RASSF1A is a proapoptotic Ras effector involved in the DNA damage response (DDR).

Purpose of the Study:

  • To investigate the role of RASSF1A in DNA repair processes beyond its known function in DDR.
  • To elucidate the interaction between RASSF1A and the DNA repair protein xeroderma pigmentosum A (XPA).

Main Methods:

  • Assessing DNA repair capacity in RASSF1A-deficient cells.
  • Analyzing the interaction between RASSF1A and XPA using protein complex formation assays.
  • Investigating the impact of a cancer-associated RASSF1A single-nucleotide polymorphism (SNP) on XPA binding and DNA repair.
  • Examining the regulation of XPA acetylation and its effect on repair complex stability.

Main Results:

  • RASSF1A forms a DNA damage-regulated complex with XPA, essential for XPA's full repair activity.
  • RASSF1A-deficient cells show impaired DNA repair.
  • A cancer-associated RASSF1A SNP variant alters XPA binding, inhibits DNA repair, and differentially regulates XPA acetylation.
  • The SNP variant hyperstabilizes the XPA-RPA70 complex, affecting DNA repair dynamics.

Conclusions:

  • RASSF1A plays a critical role in DNA repair, in addition to its function in apoptotic DDR.
  • RASSF1A regulates DNA repair through its interaction with XPA and modulation of XPA acetylation.
  • RASSF1A may coordinate the balance between DNA repair and cell death pathways in response to DNA damage.

More Related Videos

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

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

Published on: April 28, 2021

3.5K
Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

10.1K

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...
8.4K
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...
2.3K
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...
4.0K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
5.7K
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...
4.5K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
33.4K