title: Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres and maintains telomere G-overhangs.
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. Cancer Res; 75(5); 858-69. ©2015 AACR.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, Texas.
authors.forename: Raj K
authors.initials: RK
authors.lastname: Pandita
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Chow
authors.affiliation: Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, Texas. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Durga
authors.initials: D
authors.lastname: Udayakumar
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Bain
authors.affiliation: School of Science and Health, University of Western Sydney, Sydney, Australia.
authors.forename: Liza
authors.initials: L
authors.lastname: Cubeddu
authors.affiliation: Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, Texas. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Clayton R
authors.initials: CR
authors.lastname: Hunt
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, Texas. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Horikoshi
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.
authors.forename: Kum Kum
authors.initials: KK
authors.lastname: Khanna
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas. Center for Excellence in Genomics Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. tpandita@houstonmethodist.org jerry.shay@utsouthwestern.edu.
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
authors.affiliation: Department of Radiation Oncology, The Houston Methodist Research Institute, Houston, Texas. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. tpandita@houstonmethodist.org jerry.shay@utsouthwestern.edu.
authors.forename: Tej K
authors.initials: TK
authors.lastname: Pandita
mesh_terms: D000818:Animals; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism; D011485:Protein Binding; D016196:S Phase / Q000502:physiology; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C504091:NABP2 protein, human; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase