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Molecular and Cellular Biology, January 2007, p. 568-578, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.00731-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Abnormality in Initiation Program of DNA Replication Is Monitored by the Highly Repetitive rRNA Gene Array on Chromosome XII in Budding Yeast ^,

Satoru Ide,¹ Keiichi Watanabe,^1, Hiromitsu Watanabe,¹ Katsuhiko Shirahige,^1, Takehiko Kobayashi,² and Hisaji Maki^1*

Department of Molecular Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan,¹ National Institute of Basic Biology and SOKENDAI, Okazaki, Aichi 444-8585, Japan²

Received 27 April 2006/ Returned for modification 22 May 2006/ Accepted 30 October 2006

We have shown previously that perturbation of origin firing in chromosome replication causes DNA lesions and triggers DNA damage checkpoint control, which ensures genomic integrity by stopping cell cycle progression until the lesions are repaired or by inducing cell death if they are not properly repaired. This was based on the observation that the temperature-sensitive phenotype of orc1-4 and orc2-1 mutants required a programmed action of the RAD9-dependent DNA damage checkpoint. Here, we report that DNA lesions in the orc mutants are induced much more quickly and frequently within the rRNA gene (rDNA) locus than at other chromosomal loci upon temperature shift. orc mutant cells with greatly reduced rDNA copy numbers regained the ability to grow at restrictive temperatures, and the checkpoint response after the temperature shift became weak in these cells. In orc2-1 cells, completion of chromosomal duplication was delayed specifically on chromosome XII, where the rDNA array is located, and the delay was partially suppressed when the rDNA copy number was reduced. These results suggest that the rDNA locus primarily signals abnormalities in the initiation program to the DNA damage checkpoint and that the rDNA copy number modulates the sensitivity of this monitoring function.

Published ahead of print on 13 November 2006.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Cancer Research United Kingdom, London Research Institute, Clare Hall Laboratories, South Mimms, Potters Bar EN6 3LD, United Kingdom.

Present address: Tokyo Institute of Technology, Center for Biological Resources and Informatics, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.

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