Signatures of DNA double strand breaks produced in irradiated G1 and G2 cells persist into mitosis.
We have observed that some of the DNA damage or damage product caused by irradiation of interphase cells persisted throughout the cell cycle, and resulted in the expression of gamma-H2AX foci on the mitotic chromosomes. These mitotic expressions of damage after gamma-irradiation of G1 or G2 phase cells were compared in wild-type CHO and their DNA repair deficient XR-1 and UV-1 cells. gamma-H2AX foci were located on one of the chromatids or on both chromatids as isolocus paired foci. DNA double strand break (DSB) repair deficient XR-1 cells exhibited greater persistence of gamma-H2AX foci than wild-type cells when irradiated at G1 phase. Delayed subculture after irradiation significantly reduced the persistence of damage in mitotic cells and the radiosensitivity in wild-type cells, but this was not the case for XR-1 cells. Interestingly, UV and crosslinking agents sensitive UV-1 cells which show similar sensitivity to gamma-irradiation as wild-type cells by gamma-irradiation, exhibited significantly higher gamma-H2AX persistence at mitosis when they were irradiated in G1-phase but not in G2-phase. One interpretation of this is that it is due to DNA damage accumulating at stalled replication forks. As in wild type cells, in delayed subculture after gamma-ray exposure of UV-1 cells, a reduced number of foci was also seen. Our results suggest that the persistence of gamma-H2AX foci does not always correspond with the radiosensitivities of cells, but rather depends on cells' ability to repair the different kinds of DNA damages. J. Cell. Physiol. 219: 760-765, 2009. (c) 2009 Wiley-Liss, Inc.
Kato
Takamitsu A
TA
Department of Environmental & Radiological Sciences, Colorado State University, Ft. Collins, Colorado.
Okayasu
Ryuichi
R
Bedford
Joel S
JS
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair; D016193:G1 Phase / Q000235:genetics* / Q000528:radiation effects*; D016195:G2 Phase / Q000235:genetics* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D006657:Histones / Q000378:metabolism / Q000528:radiation effects; D008938:Mitosis / Q000235:genetics* / Q000528:radiation effects*; D010766:Phosphorylation
D006657:Histones