HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dang, T. Articles by Wang, X.-F. Search for Related Content PubMed PubMed Citation Articles by Dang, T. Articles by Wang, X.-F.

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA

In response to DNA damage or replication block, cells activate a battery of checkpoint signaling cascades to control cell cycle progression and elicit DNA repair in order to maintain genomic stability and integrity. Identified as a homolog of its fission yeast counterpart, human Rad9 was proposed to form a Rad9-Hus1-Rad1 protein complex to mediate checkpoint signals. However, the precise function of Rad9 in the process of checkpoint activation is not fully understood. Using the RNA interference technique, we investigated the role of Rad9 in the genotoxic stress-induced activation of S-phase checkpoint and the maintenance of chromosomal stability. We found that Rad9 knockdown reduced the phosphorylation of Rad17, Chk1 and Smc1 in response to DNA replication block and certain types of DNA damage. Immunofluorescence studies showed that the removal of Rad9 disrupted the foci formation of phosphorylated Chk1, but not ATR. Moreover, Rad9 knockdown resulted in radioresistant DNA synthesis and reduced cell viability under replication stress. Finally, removal of Rad9 by RNAi led to increased accumulation of spontaneous chromosomal aberrations. Taken together, these results suggest a critical and specific role of Rad9 in the activation of S-phase checkpoint and the maintenance of chromosome stability.

*Correspondence: E-mail: wang0011{at}mc.duke.edu

This article has been cited by other articles:

				Z. Hu, Y. Liu, C. Zhang, Y. Zhao, W. He, L. Han, L. Yang, K. M. Hopkins, X. Yang, H. B. Lieberman, et al. Targeted Deletion of Rad9 in Mouse Skin Keratinocytes Enhances Genotoxin-Induced Tumor Development Cancer Res., July 15, 2008; 68(14): 5552 - 5561. [Abstract] [Full Text] [PDF]

				H. Niida, Y. Katsuno, B. Banerjee, M. P. Hande, and M. Nakanishi Specific Role of Chk1 Phosphorylations in Cell Survival and Checkpoint Activation Mol. Cell. Biol., April 1, 2007; 27(7): 2572 - 2581. [Abstract] [Full Text] [PDF]

				K. Zaugg, Y.-W. Su, P. T. Reilly, Y. Moolani, C. C. Cheung, R. Hakem, A. Hirao, Q. Liu, S. J. Elledge, and T. W. Mak Cross-talk between Chk1 and Chk2 in double-mutant thymocytes PNAS, March 6, 2007; 104(10): 3805 - 3810. [Abstract] [Full Text] [PDF]

				R. K. Pandita, G. G. Sharma, A. Laszlo, K. M. Hopkins, S. Davey, M. Chakhparonian, A. Gupta, R. J. Wellinger, J. Zhang, S. N. Powell, et al. Mammalian rad9 plays a role in telomere stability, s- and g2-phase-specific cell survival, and homologous recombinational repair. Mol. Cell. Biol., March 1, 2006; 26(5): 1850 - 1864. [Abstract] [Full Text] [PDF]

				H. Ishii, T. Inageta, K. Mimori, T. Saito, H. Sasaki, M. Isobe, M. Mori, C. M. Croce, K. Huebner, K. Ozawa, et al. Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis PNAS, July 5, 2005; 102(27): 9655 - 9660. [Abstract] [Full Text] [PDF]