G4 DNA in ras genes and its potential in cancer therapy

Susanna Cogoi1, Luigi E Xodo1

  • 1Department of Medical and Biological Sciences, University of Udine, P.le Kolbe 4, 33100 Udine, Italy.

Insights

G-quadruplexes are DNA structures found in human genes, including cancer-linked ras genes. This review explores their role in gene regulation and potential as anticancer drug targets.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The human genome contains canonical double helix DNA alongside G-quadruplex structures.
  • G-quadruplexes play significant biological roles.
  • Ras genes are frequently mutated in human cancers.

Purpose of the Study:

  • To review current knowledge on G-quadruplex formation in ras gene promoters.
  • To discuss nuclear proteins that recognize G-quadruplexes and their role in transcription.
  • To examine G-quadruplexes in ras transcripts and their potential as anticancer targets.

Main Methods:

  • Literature review of G-quadruplex formation in ras genes.
  • Analysis of nuclear proteins interacting with G-quadruplexes.
  • Examination of G-quadruplexes in 5'-untranslated regions of ras transcripts.

Main Results:

  • G-quadruplexes form in the promoters of ras genes, implicated in ~30% of human cancers.
  • Specific nuclear proteins recognize these DNA structures, influencing transcription.
  • G-quadruplexes are also found in the 5'-untranslated region of ras transcripts.

Conclusions:

  • Ras G-quadruplexes and their binding proteins are promising targets for novel anticancer small molecules.
  • Targeting these structures offers a potential strategy for cancer therapy.

Related Concept Videos

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...
7.5K
The Ras Gene02:38

The Ras Gene

2.5K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.7K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
6.6K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

5.9K
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...
5.4K