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Molecular and Cellular Biology, January 2009, p. 471-482, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.01352-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Functional Dissection of Human and Mouse POT1 Proteins {triangledown} ,{dagger}

Wilhelm Palm,{ddagger} Dirk Hockemeyer,§ Tatsuya Kibe, and Titia de Lange*

Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, New York 10065

Received 25 August 2008/ Returned for modification 8 October 2008/ Accepted 20 October 2008

The single-stranded telomeric DNA binding protein POT1 protects mammalian chromosome ends from the ATR-dependent DNA damage response, regulates telomerase-mediated telomere extension, and limits 5'-end resection at telomere termini. Whereas most mammals have a single POT1 gene, mice have two POT1 proteins that are functionally distinct. POT1a represses the DNA damage response, and POT1b controls 5'-end resection. In contrast, as we report here, POT1a and POT1b do not differ in their ability to repress telomere recombination. By swapping domains, we show that the DNA binding domain of POT1a specifies its ability to repress the DNA damage response. However, no differences were detected in the in vitro DNA binding features of POT1a and POT1b. In contrast to the repression of ATR signaling by POT1a, the ability of POT1b to control 5'-end resection was found to require two regions in the C terminus, one corresponding to the TPP1 binding domain and a second representing a new domain located between amino acids (aa) 300 and 350. Interestingly, the DNA binding domain of human POT1 can replace that of POT1a to repress ATR signaling, and the POT1b region from aa 300 to 350 required for the regulation of the telomere terminus is functionally conserved in human POT1. Thus, human POT1 combines the features of POT1a and POT1b.

* Corresponding author. Mailing address: Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065-6399. Phone: (212) 327-8146. Fax: (212) 327-7147. E-mail: delange{at}mail.rockefeller.edu

{triangledown} Published ahead of print on 27 October 2008.

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

{ddagger} Present address: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.

§ Present address: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Boston, MA 02142.

Molecular and Cellular Biology, January 2009, p. 471-482, Vol. 29, No. 2
0270-7306/09/$08.00+0     doi:10.1128/MCB.01352-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shakirov, E. V., Song, X., Joseph, J. A., Shippen, D. E. (2009). POT1 proteins in green algae and land plants: DNA-binding properties and evidence of co-evolution with telomeric DNA. Nucleic Acids Res 0: gkp785v1-gkp785 [Abstract] [Full Text]  


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