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Molecular and Cellular Biology, August 2007, p. 5898-5909, Vol. 27, No. 16
0270-7306/07/$08.00+0     doi:10.1128/MCB.00603-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Telomere Maintenance through Spatial Control of Telomeric Proteins{triangledown}

Liuh-Yow Chen, Dan Liu, and Zhou Songyang*

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

Received 4 April 2007/ Returned for modification 1 May 2007/ Accepted 27 May 2007

The six human telomeric proteins TRF1, TRF2, RAP1, TIN2, POT1, and TPP1 can form a complex called the telosome/shelterin, which is required for telomere protection and length control. TPP1 has been shown to regulate both POT1 telomere localization and telosome assembly through its binding to TIN2. It remains to be determined where such interactions take place and whether cellular compartmentalization of telomeric proteins is important for telomere maintenance. We systematically investigated here the cellular localization and interactions of human telomeric proteins. Interestingly, we found TIN2, TPP1, and POT1 to localize and interact with each other in both the cytoplasm and the nucleus. Unexpectedly, TPP1 contains a functional nuclear export signal that directly controls the amount of TPP1 and POT1 in the nucleus. Furthermore, binding of TIN2 to TPP1 promotes the nuclear localization of TPP1 and POT1. We also found that disrupting TPP1 nuclear export could result in telomeric DNA damage response and telomere length disregulation. Our findings highlight how the coordinated interactions between TIN2, TPP1, and POT1 in the cytoplasm regulate the assembly and function of the telosome in the nucleus and indicate for the first time the importance of nuclear export and spatial control of telomeric proteins in telomere maintenance.

* Corresponding author. Mailing address: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-5220. Fax: (713) 796-9438. E-mail: songyang{at}bcm.tmc.edu

{triangledown} Published ahead of print on 11 June 2007.

Molecular and Cellular Biology, August 2007, p. 5898-5909, Vol. 27, No. 16
0270-7306/07/$08.00+0     doi:10.1128/MCB.00603-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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