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Molecular and Cellular Biology, February 2005, p. 1070-1080, Vol. 25, No. 3
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.3.1070-1080.2005

POT1 and TRF2 Cooperate To Maintain Telomeric Integrity{dagger}

Qin Yang, Yun-Ling Zheng, and Curtis C. Harris*

Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Received 22 June 2004/ Returned for modification 18 July 2004/ Accepted 14 October 2004

Mammalian telomeric DNA contains duplex TTAGGG repeats and single-stranded overhangs. POT1 (protection of telomeres 1) is a telomere-specific single-stranded DNA-binding protein, highly conserved in eukaryotes. The biological function of human POT1 is not well understood. In the present study, we demonstrate that POT1 plays a key role in telomeric end protection. The reduction of POT1 by RNA interference led to the loss of telomeric single-stranded overhangs and induced apoptosis, chromosomal instability, and senescence in cells. POT1 and TRF2 interacted with each other to form a complex with telomeric DNA. A dominant negative TRF2, TRF2{Delta}B{Delta}M, bound to POT1 and prevented it from binding to telomeres. POT1 overexpression protected against TRF2{Delta}B{Delta}M-induced loss of telomeric single-stranded overhangs, chromosomal instability, and senescence. These results demonstrate that POT1 and TRF2 share in part in the same pathway for telomere capping and suggest that POT1 binds to the telomeric single-stranded DNA in the D-loop and cooperates with TRF2 in t-loop maintenance.

* Corresponding author. Mailing address: Laboratory of Human Carcinogenesis, NCI, NIH, Bldg. 37, Rm. 3068, 37 Convent Dr., Bethesda, MD 20892-4255. Phone: (301) 496-2048. Fax: (301) 496-0497. E-mail: Curtis_Harris{at}nih.gov.

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

Molecular and Cellular Biology, February 2005, p. 1070-1080, Vol. 25, No. 3
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.3.1070-1080.2005




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