S-phase cells are more sensitive to high-linear energy transfer radiation

Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):1236-41. doi: 10.1016/j.ijrobp.2008.12.089.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism*
  • DNA / metabolism*
  • DNA Repair
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Radiation
  • G2 Phase / physiology
  • G2 Phase / radiation effects
  • Ku Autoantigen
  • Linear Energy Transfer*
  • Mice
  • Phenotype
  • Radiation Tolerance*
  • S Phase / physiology
  • S Phase / radiation effects*

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • DNA
  • Xrcc6 protein, mouse
  • Ku Autoantigen