Potential role of DNA-dependent protein kinase in cellular resistance to ionizing radiation

LOW ENERGY ACCELERATOR, RAY TECHNOLOGY AND APPLICATIONS

Potential role of DNA-dependent protein kinase in cellular resistance to ionizing radiation

LI Ning，

ZHANG Hong，

WANG Yanling，

WANG Xiaohu，

HAO Jifang

Nuclear Science and Techniques

Vol.20, No.2

pp.87-92

Published in print 20 Apr 2009

DOI：10.13538/j.1001-8042/nst.20.87-92

28600

In this paper, we study the ability of DNA-PK-deficient (M059J) and -proficient (M059K) cells to undergo the rate of cellular proliferation, cell cycle distribution and apoptosis after 10 Gy X-ray irradiation, and the role of DNA-PK in radiosensitivity. The results showed that M059J cells exhibited hyper-radiosensitivity compared with M059K cells. A strong G2 phase arrest was observed in M059J cells post irradiation. Significant accumulation in the G2 phase in M059J cells was accompanied by apoptosis at 12 h. Altogether, the data suggested that DNA-PK may have two roles in mammalian cells after DNA damage, a role in DNA DSB repair and a second role in DNA-damaged cells to traverse a G2 checkpoint, by which DNA-PK may affect cellular sensitivity to ionizing radiation.

DNA-dependent protein kinase (DNA-PK)Cell cycle checkpointApoptosisRadiosensitivity

References

[1]

Burma S, Chen D J. DNA Repair (Amst), 2004, 3: 909-918.

[2]

Jeggo P A. Radiat Res, 1998, 150: S80-S91.

[3]

DiBiase S J, Zeng Z C, Chen R, et al. Cancer Res, 2000, 60: 1245-1253.

[4]

Iliakis G, Wang H, Perrault AR, et al. Cytogenet Genome Res, 2004, 104: 14-20.

[5]

Smith G C, Jackson S P. Genes Dev, 1999, 13: 916-934.

[6]

Shiloh Y. Nat Rev Cancer, 2003, 3: 155-168.

[7]

Chan D W, Chen B P, Prithivirajsingh S, et al. Genes Dev, 2002, 16: 2333-2338.

[8]

Ding Q, Reddy Y V, Wang W, et al. Mol Cell Biol, 2003, 23: 5836-5848.

[9]

Woo R A, Jack M T, Xu Y, et al. EMBO J, 2002, 21: 3000-3008.

[10]

Wang S, Guo M, Ouyang H, et al. Proc Natl Acad Sci USA, 2000, 97: 1584-1588.

[11]

Candéias S M, Durum SK, Muegge K. Biochimie, 1997, 79: 607-612.

[12]

Gurley K E, Vo K, Kemp C J. Cancer Res, 1998, 58: 3111-3115.

[13]

Danial N N, Korsmeyer S J. Cell, 2004, 116: 205-219.

[14]

Strasser A, O'Connor L, Dixit V M. Annu Rev Biochem, 2000, 69: 217-245.

[15]

Hanahan D, Weinberg R A. Cell, 2000, 100: 57-70.

[16]

Jäättelä M. Oncogene, 2004, 23: 2746-2756.

[17]

Cryns V, Yuan J. Genes Dev, 1998, 12: 1551-1570.

[18]

Los M, Wesselborg S, Schulze-Osthoff K. Immunity, 1999, 10: 629-639.

[19]

Allalunis-Turner M J, Barron G M, Day R S, et al. Radiat Res, 1993, 134: 349-354.

[20]

Hosoi Y, Miyachi H, Matsumoto Y, et al. Int J Cancer, 1998, 78: 642-647.

[21]

Solly K, Wang X, Xu X, et al. Assay Drug Dev Technol, 2004, 2: 363-372.

[22]

Decker P, Muller S. Curr Pharm Biotechnol, 2002, 3: 275-283.

[23]

Soldani C, Scovassi A I. Apoptosis, 2002, 7: 321-328.

[24]

Duriez P J, Shah G M. Biochem Cell Biol, 1997, 75: 337-349.

[25]

Allalunis-Turner M J, Zia P K, Barron G M, et al. Radiat Res, 1995, 144: 288-293.

[26]

Lee S E, Mitchell R A, Cheng A, et al. Mol Cell Biol, 1997, 17: 1425-1433.

[27]

Nilsson A, Sirzén F, Lewensohn R, et al. Cell Prolif, 1999, 32: 239-248.

[28]

Holgersson A, Jernberg A R, Persson L M, et al. Int J Radiat Biol, 2003, 79: 611-621.

[29]

Holgersson A, Heiden T, Castro J, et al. Int J Radiat Oncol Biol Phys, 2005, 61: 915-921.

[30]

Takata M, Sasaki M S, Sonoda E, et al. EMBO J, 1998, 17: 5497-5508.

[31]

Stenerlöw B, Karlsson K H, Cooper B, et al. Radiat Res, 2003, 159: 502-510.

[32]

Yoshida M, Hosoi Y, Miyachi H, et al. Int J Radiat Biol, 2002, 78: 503-512.