Fluorescence spectroscopic detection and measurement of single telomere molecules

Cyrus W. Beh; Ye Zhang; Yun Ling Zheng; Bing Sun; Tza Huei Wang

doi:10.1093/nar/gky627

Fluorescence spectroscopic detection and measurement of single telomere molecules

Cyrus W. Beh, Ye Zhang, Yun Ling Zheng, Bing Sun, Tza Huei Wang

Whiting School of Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Telomeres are the end-caps of chromosomes that serve to protect the integrity of the genome. Below certain critical lengths, the telomeres can no longer fulfill their protective function, and chromosomal instability ensues. Telomeres shorten during normal cell division due to the end replication problem and are implicated in the development of various aging-associated diseases, including cancer. Telomere length has the potential to serve as a useful biomarker in the field of aging and cancer. However, existing methods of telomere measurement are either too laborious, unable to provide absolute measurement of individual telomere lengths, or limited to certain chromosomes or cell types. Here, we describe an easy single-molecule, fluorescence spectroscopic method for measuring the length of telomeres that permits the profiling of absolute telomere lengths in any DNA sample. We have demonstrated the accurate detection of telomeres as short as 100 bp using cloned telomere standards, and have profiled telomere lengths in human cancer cell lines and primary cells. Since this method allows direct comparison between samples, it could greatly improve the clinical utility of telomere biomarkers.

Original language	English (US)
Article number	e117
Journal	Nucleic acids research
Volume	46
Issue number	19
DOIs	https://doi.org/10.1093/nar/gky627
State	Published - Nov 2 2018

ASJC Scopus subject areas

Genetics

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10.1093/nar/gky627

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title = "Fluorescence spectroscopic detection and measurement of single telomere molecules",

abstract = "Telomeres are the end-caps of chromosomes that serve to protect the integrity of the genome. Below certain critical lengths, the telomeres can no longer fulfill their protective function, and chromosomal instability ensues. Telomeres shorten during normal cell division due to the end replication problem and are implicated in the development of various aging-associated diseases, including cancer. Telomere length has the potential to serve as a useful biomarker in the field of aging and cancer. However, existing methods of telomere measurement are either too laborious, unable to provide absolute measurement of individual telomere lengths, or limited to certain chromosomes or cell types. Here, we describe an easy single-molecule, fluorescence spectroscopic method for measuring the length of telomeres that permits the profiling of absolute telomere lengths in any DNA sample. We have demonstrated the accurate detection of telomeres as short as 100 bp using cloned telomere standards, and have profiled telomere lengths in human cancer cell lines and primary cells. Since this method allows direct comparison between samples, it could greatly improve the clinical utility of telomere biomarkers.",

author = "Beh, {Cyrus W.} and Ye Zhang and Zheng, {Yun Ling} and Bing Sun and Wang, {Tza Huei}",

note = "Funding Information: National Institutes of Health [R01CA155305, R21CA186809, R44GM103356, R01AI117032 to T.H.W. and R01CA132996 to Y.L.Z.]; Agency for Science, Technology and Research Singapore (A*STAR Scholarship to C.W.B.). Funding for open access charge: National Institutes of Health. Conflict of interest statement. None declared. Funding Information: National Institutes of Health [R01CA155305, R21CA186809, R44GM103356, R01AI117032 to T.H.W. and R01CA132996 to Y.L.Z.]; Agency for Science, Technology and Research Singapore (A*STAR Scholarship to C.W.B.). Funding for open access charge: National Institutes of Health. Publisher Copyright: {\textcopyright} The Author(s) 2018.",

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doi = "10.1093/nar/gky627",

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AU - Beh, Cyrus W.

AU - Zhang, Ye

AU - Zheng, Yun Ling

AU - Sun, Bing

AU - Wang, Tza Huei

N1 - Funding Information: National Institutes of Health [R01CA155305, R21CA186809, R44GM103356, R01AI117032 to T.H.W. and R01CA132996 to Y.L.Z.]; Agency for Science, Technology and Research Singapore (A*STAR Scholarship to C.W.B.). Funding for open access charge: National Institutes of Health. Conflict of interest statement. None declared. Funding Information: National Institutes of Health [R01CA155305, R21CA186809, R44GM103356, R01AI117032 to T.H.W. and R01CA132996 to Y.L.Z.]; Agency for Science, Technology and Research Singapore (A*STAR Scholarship to C.W.B.). Funding for open access charge: National Institutes of Health. Publisher Copyright: © The Author(s) 2018.

PY - 2018/11/2

Y1 - 2018/11/2

N2 - Telomeres are the end-caps of chromosomes that serve to protect the integrity of the genome. Below certain critical lengths, the telomeres can no longer fulfill their protective function, and chromosomal instability ensues. Telomeres shorten during normal cell division due to the end replication problem and are implicated in the development of various aging-associated diseases, including cancer. Telomere length has the potential to serve as a useful biomarker in the field of aging and cancer. However, existing methods of telomere measurement are either too laborious, unable to provide absolute measurement of individual telomere lengths, or limited to certain chromosomes or cell types. Here, we describe an easy single-molecule, fluorescence spectroscopic method for measuring the length of telomeres that permits the profiling of absolute telomere lengths in any DNA sample. We have demonstrated the accurate detection of telomeres as short as 100 bp using cloned telomere standards, and have profiled telomere lengths in human cancer cell lines and primary cells. Since this method allows direct comparison between samples, it could greatly improve the clinical utility of telomere biomarkers.

AB - Telomeres are the end-caps of chromosomes that serve to protect the integrity of the genome. Below certain critical lengths, the telomeres can no longer fulfill their protective function, and chromosomal instability ensues. Telomeres shorten during normal cell division due to the end replication problem and are implicated in the development of various aging-associated diseases, including cancer. Telomere length has the potential to serve as a useful biomarker in the field of aging and cancer. However, existing methods of telomere measurement are either too laborious, unable to provide absolute measurement of individual telomere lengths, or limited to certain chromosomes or cell types. Here, we describe an easy single-molecule, fluorescence spectroscopic method for measuring the length of telomeres that permits the profiling of absolute telomere lengths in any DNA sample. We have demonstrated the accurate detection of telomeres as short as 100 bp using cloned telomere standards, and have profiled telomere lengths in human cancer cell lines and primary cells. Since this method allows direct comparison between samples, it could greatly improve the clinical utility of telomere biomarkers.

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Fluorescence spectroscopic detection and measurement of single telomere molecules

Abstract

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