Document Detail

S-phase cells are more sensitive to high-linear energy transfer radiation.
MedLine Citation:
PMID:  19545789     Owner:  NLM     Status:  MEDLINE    
PURPOSE: S-phase cells are more resistant to low-linear energy transfer (LET) ionizing radiation (IR) than nonsynchronized and G(1)-phase cells, because both nonhomologous end-joining (NHEJ) and homologous recombination repair can repair DNA double-strand breaks (DSBs) in the S phase. Although it was reported 3 decades ago that S-phase cells did not show more resistance to high-LET IR than cells in other phases, the mechanism remains unclear. We therefore attempted to study the phenotypes and elucidate the mechanism involved. METHODS AND MATERIALS: Wild-type and NHEJ-deficient cell lines were synchronized using the double-thymidine approach. A clonogenic assay was used to detect the sensitivity of nonsynchronized, synchronized S-phase, and G(2)-phase cells to high- and low-LET IR. The amounts of Ku bound to DSBs in the high- and low-LET-irradiated cells were also examined. RESULTS: S-phase wild-type cells (but not NHEJ-deficient cells) were more sensitive to high-LET IR than nonsynchronized and G(2)-phase cells. In addition, S-phase wild-type cells showed less efficient Ku protein binding to DSBs than nonsynchronized and G(2)-phase cells in response to high-LET IR, although all cells at all phases showed similarly efficient levels of Ku protein binding to DSBs in response to low-LET IR. CONCLUSIONS: S-phase cells are more sensitive to high-LET IR than nonsynchronized and G(2)-phase cells, because of the following mechanism: it is more difficult for Ku protein to bind to high-LET IR-induced DNA DSBs in S-phase cells than in cells at other phases, which results in less efficient NHEJ.
Hongyan Wang; Shuang Liu; Piyan Zhang; Shimeng Zhang; Mamta Naidu; Huichen Wang; Ya Wang
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  International journal of radiation oncology, biology, physics     Volume:  74     ISSN:  1879-355X     ISO Abbreviation:  Int. J. Radiat. Oncol. Biol. Phys.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-23     Completed Date:  2009-07-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603616     Medline TA:  Int J Radiat Oncol Biol Phys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1236-41     Citation Subset:  IM    
Department of Radiation Oncology and Kimmel Cancer Center of Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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MeSH Terms
Antigens, Nuclear / metabolism*
DNA / metabolism*
DNA Repair
DNA-Binding Proteins / metabolism*
Dose-Response Relationship, Radiation
G2 Phase / physiology,  radiation effects
Linear Energy Transfer*
Radiation Tolerance*
S Phase / physiology,  radiation effects*
Reg. No./Substance:
0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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