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PMID:25589350

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Citation

Pandita, RK, Chow, TT, Udayakumar, D, Bain, AL, Cubeddu, L, Hunt, CR, Shi, W, Horikoshi, N, Zhao, Y, Wright, WE, Khanna, KK, Shay, JW and Pandita, TK (2015) Single-strand DNA-binding protein SSB1 facilitates TERT recruitment to telomeres and maintains telomere G-overhangs. Cancer Res. 75:858-69

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.

Links

PubMed PMC4351820 Online version:10.1158/0008-5472.CAN-14-2289

Keywords

Animals; DNA Damage; DNA, Single-Stranded/metabolism; DNA-Binding Proteins/metabolism; HCT116 Cells; HEK293 Cells; Humans; Mice; Mice, Knockout; Mitochondrial Proteins/metabolism; Protein Binding; S Phase/physiology; Telomerase/metabolism; Telomere/metabolism; Telomeric Repeat Binding Protein 1/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TERT

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9BQ15

F

Seeded From UniProt

complete

HUMAN:TERT

located_in

GO:0000781: chromosome, telomeric region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TERT

involved_in

GO:0070200: establishment of protein localization to telomere

ECO:0000314: direct assay evidence used in manual assertion

P

  • transports_or_maintains_localization_of:(UniProtKB:Q9BQ15)

Seeded From UniProt

complete

HUMAN:TERF1

involved_in

GO:1904850: negative regulation of establishment of protein localization to telomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • transports_or_maintains_localization_of:(UniProtKB:Q9BQ15)

Seeded From UniProt

complete

MOUSE:SOSB1

involved_in

GO:0006281: DNA repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SOSB1

involved_in

GO:1904355: positive regulation of telomere capping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ACD

involved_in

GO:0070200: establishment of protein localization to telomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • transports_or_maintains_localization_of:(UniProtKB:Q9BQ15)|transports_or_maintains_localization_of:(UniProtKB:O14746)

Seeded From UniProt

complete

HUMAN:SOSB1

located_in

GO:0000781: chromosome, telomeric region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SOSB1

involved_in

GO:0070200: establishment of protein localization to telomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • transports_or_maintains_localization_of:(UniProtKB:O14746)

Seeded From UniProt

complete

HUMAN:POTE1

involved_in

GO:0070200: establishment of protein localization to telomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • transports_or_maintains_localization_of:(UniProtKB:Q9BQ15)|transports_or_maintains_localization_of:(UniProtKB:O14746)

Seeded From UniProt

complete

HUMAN:TERT

involved_in

GO:0070200: establishment of protein localization to telomere

ECO:0000314: direct assay evidence used in manual assertion

P

transports_or_maintains_localization_of:(UniProtKB:Q9BQ15)

Seeded From UniProt

complete

HUMAN:TERT

part_of

GO:0000784: nuclear chromosome, telomeric region

ECO:0000314: direct assay evidence used in manual assertion

C

exists_during:(GO:0000084)

Seeded From UniProt

complete

HUMAN:SOSB1

NOT|enables

GO:0061730: C-rich strand telomeric DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SOSB1

involved_in

GO:0070200: establishment of protein localization to telomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

transports_or_maintains_localization_of:(UniProtKB:O14746)

Seeded From UniProt

complete

HUMAN:SOSB1

enables

GO:0098505: G-rich strand telomeric DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SOSB1

enables

GO:0070182: DNA polymerase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14746

F

Seeded From UniProt

complete

HUMAN:SOSB1

NOT|involved_in

GO:0051972: regulation of telomerase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SOSB1

involved_in

GO:1904355: positive regulation of telomere capping

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SOSB1

part_of

GO:0000784: nuclear chromosome, telomeric region

ECO:0000314: direct assay evidence used in manual assertion

C

exists_during:(GO:0000084)

Seeded From UniProt

complete

HUMAN:POTE1

involved_in

GO:0070200: establishment of protein localization to telomere

ECO:0000315: mutant phenotype evidence used in manual assertion

P

transports_or_maintains_localization_of:(UniProtKB:Q9BQ15)|transports_or_maintains_localization_of:(UniProtKB:O14746)

Seeded From UniProt

complete

Notes

See also

References

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