A loss of function screen identifies nine new radiation susceptibility genes.

Abstract

Genomic instability is considered a hallmark of carcinogenesis, and dysfunction of DNA repair and cell cycle regulation in response to DNA damage caused by ionizing radiation are thought to be important factors in the early stages of genomic instability. We performed cell-based functional screening using an RNA interference library targeting 200 genes in human cells. We identified three known and nine new radiation susceptibility genes, eight of which are linked directly or potentially with cell cycle progression. Cell cycle analysis on four of the genes not previously linked to cell cycle progression demonstrated that one, ZDHHC8, was associated with the G2/M checkpoint in response to DNA damage. Further study of the 12 radiation susceptibility genes identified in this screen may help to elucidate the molecular mechanisms of cell cycle progression, DNA repair, cell death, cell growth and genomic instability, and to develop new radiation sensitizing agents for radiotherapy.

• Authors: Hitomi Sudo, Atsushi B Tsuji, Aya Sugyo, Takashi Imai, Tsuneo Saga, Yoshi-nobu Harada
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 364 Issue 3 Pg. 695-701 (Dec 21 2007) ISSN: 1090-2104 [Electronic] United States
• PMID: 17964541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Proteome

Topics

• Cell Cycle Proteins (metabolism)
• Cell Line
• DNA Damage (physiology)
• DNA Repair (physiology, radiation effects)
• Humans
• Kidney (metabolism, radiation effects)
• Proteome (metabolism)
• Radiation Tolerance (genetics)