Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres and maintains telomere G-overhangs

Raj K. Pandita, Tracy T. Chow, Durga Udayakumar, Amanda L. Bain, Liza Cubeddu, Clayton R. Hunt, Wei Shi, Nobuo Horikoshi, Yong Zhao, Woodring E. Wright, Kum Kum Khanna, Jerry W. Shay, Tej K. Pandita

Research output: Contribution to journalArticle

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Abstract

Proliferating mammalian stem and cancer cells express telomerase [telomerase reverse transcriptase (TERT)] in an effort to extend chromosomal G-overhangs and maintain telomere ends. Telomerase-expressing cells also have higher levels of the single-stranded DNA-binding protein SSB1, which has a critical role in DNA double-strand break (DSB) repair. Here, we report that SSB1 binds specifically to G-strand telomeric DNA in vitro and associates with telomeres in vivo. SSB1 interacts with the TERT catalytic subunit and regulates its interaction with telomeres. Deletion of SSB1 reduces TERT interaction with telomeres and leads to G-overhang loss. Although SSB1 is recruited to DSB sites, we found no corresponding change in TERT levels at these sites, implying that SSB1-TERT interaction relies upon a specific chromatin structure or context. Our findings offer an explanation for how telomerase is recruited to telomeres to facilitate G-strand DNA extension, a critical step in maintaining telomere ends and cell viability in all cancer cells.

Original languageEnglish (US)
Pages (from-to)858-869
Number of pages12
JournalCancer Research
Volume75
Issue number5
DOIs
StatePublished - Mar 1 2015

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Telomerase
Telomere
DNA-Binding Proteins
Double-Stranded DNA Breaks
Neoplastic Stem Cells
DNA
Chromatin
Cell Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres and maintains telomere G-overhangs. / Pandita, Raj K.; Chow, Tracy T.; Udayakumar, Durga; Bain, Amanda L.; Cubeddu, Liza; Hunt, Clayton R.; Shi, Wei; Horikoshi, Nobuo; Zhao, Yong; Wright, Woodring E.; Khanna, Kum Kum; Shay, Jerry W.; Pandita, Tej K.

In: Cancer Research, Vol. 75, No. 5, 01.03.2015, p. 858-869.

Research output: Contribution to journalArticle

Pandita, RK, Chow, TT, Udayakumar, D, Bain, AL, Cubeddu, L, Hunt, CR, Shi, W, Horikoshi, N, Zhao, Y, Wright, WE, Khanna, KK, Shay, JW & Pandita, TK 2015, 'Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres and maintains telomere G-overhangs', Cancer Research, vol. 75, no. 5, pp. 858-869. https://doi.org/10.1158/0008-5472.CAN-14-2289
Pandita, Raj K. ; Chow, Tracy T. ; Udayakumar, Durga ; Bain, Amanda L. ; Cubeddu, Liza ; Hunt, Clayton R. ; Shi, Wei ; Horikoshi, Nobuo ; Zhao, Yong ; Wright, Woodring E. ; Khanna, Kum Kum ; Shay, Jerry W. ; Pandita, Tej K. / Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres and maintains telomere G-overhangs. In: Cancer Research. 2015 ; Vol. 75, No. 5. pp. 858-869.
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