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Cytogenetic Response to Ionizing Radiation Exposure in Human Fibroblasts with Suppressed Expression of Non-DSB Repair GenesChanges of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in double-strand break (DSB) repair, and its impact on cytogenetic responses has not been well studied. The purpose of this study is to identify new roles of IR inducible genes in radiation-induced chromosome aberrations and micronuclei formation. In the study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by small interfering RNA in human fibroblast cells. Frequencies of micronuclei (MN) formation and chromosome aberrations were measured to determine the efficiency of cytogenetic repair, and the fraction of bi-nucleated cells in the MN analysis was used as a marker for cell cycle progression. In response to gamma radiation, the formation of MN was significantly increased by suppressed expression of five genes: Ku70 (DSB repair pathway), XPA (nucleotide excision repair pathway), RPA1 (mismatch repair pathway), RAD17 and RBBP8 (cell cycle control). Knocked-down expression of four genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Moreover, decreased XPA, p21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Nine of these eleven genes, whose knock-down expression affected cytogenetic repair, were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate IR-induced biological consequences. Furthermore, eight non-DBS repair genes showed involvement in regulating DSB repair, indicating that successful DSB repair requires both DSB repair mechanisms and non-DSB repair systems.
Document ID
20090014196
Document Type
Conference Paper
Authors
Zhang, Ye (NASA Johnson Space Center Houston, TX, United States)
Rohde, Larry H. (Houston Univ.-Clear Lake Houston, TX, United States)
Emami, Kamal (NASA Johnson Space Center Houston, TX, United States)
Hammond, Dianne (NASA Johnson Space Center Houston, TX, United States)
Mehta, Satish K. (NASA Johnson Space Center Houston, TX, United States)
Jeevarajan, Antony S. (NASA Johnson Space Center Houston, TX, United States)
Pierson, Duane L. (NASA Johnson Space Center Houston, TX, United States)
Wu, Honglu (NASA Johnson Space Center Houston, TX, United States)
Date Acquired
August 24, 2013
Publication Date
January 1, 2009
Subject Category
Life Sciences (General)
Report/Patent Number
JSC-18121
Meeting Information
9th International Symposium on Chromosomal(Saint Goar)
Distribution Limits
Public
Copyright
Other