RAD51: The cell's 'Mr. Fix-it'

Wed, 01/09/2013 - 11:04

RAD51 is a recombinase protein encoded by RAD51 gene in humans. Human RAD51 family members are highly similar to bacterial RecA and yeast Rad51, both biochemically and structurally. It is a 339-amino acid protein that plays an important role in homologous recombination (HR) of DNA during double-strand break (DSB) repair.

DSBs may be the most disruptive form of DNA damage. If left unrepaired, they lead to broken chromosomes and cell death. If repaired improperly, they can result in chromosome translocations and cancer (1).  Homologous recombination is the major pathway to repair DSBs during S phase to G2 phase of the cycle, using the sister chromatid as the repair template. Upon DSB formation, the broken DNA end(s) are processed and resected prior to loading of RAD51. Strand invasion by the RAD51 nucleoprotein filament produces a four-way DNA junction (or Holliday junction) which is migrated and processed to repair the damage.

IF analysis of RAD51 IF analysis of RAD51

Previous studies have shown that overexpression of RAD51 in different organisms and cell types leads to a wide range of consequences, including increased homologous recombination and increased resistance to DNA damage (2). In cultured mammalian cells, unregulated RAD51 expression enhances resistance to ionizing radiation when irradiated in late S/G2 phase of the cell cycle (3).

However, increased RAD51 levels can contribute to the development, progression and drug resistance of the cancer. Gemcitabine, an epidermal growth factor receptor-tyrosine kinase inhibitor, has been used clinically to treat patients with non-small cell lung cancer. One of the major causes of drug resistance is that Gemcitabine increases the expression of RAD51 by increasing its mRNA and protein stability (4). Using siRNA depletion of RAD51 has demonstrated to reduce drug resistance and improve Gemcitabine-induced cytotoxicity.

Loss of RAD51 function can result in an elevated mutation rate, leading to accumulation of DNA damage and potentially cause cancer. During DNA repair, RAD51 interacts directly or indirectly with a number of breast cancer susceptiblility proteins, such as BRCA1 and BRCA2. It has been shown that mutations of RAD51 gene are associated with an increased risk of developing breast cancer (5).

  1. PMID: 9305850
  2. PMID: 18243065
  3. PMID: 9611228
  4. PMID: 20855443
  5. PMID: 16762046

Novus Biologicals offers Rad51 reagents for your research needs including:


Blog Topics