Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules

Lifeng Xu, Elizabeth H. Blackburn

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

We identified and characterized a human orthologue of Rif1 protein, which in budding yeast interacts in vivo with the major duplex telomeric DNA binding protein Rap1p and negatively regulates telomere length. Depletion of hRif1 by RNA interference in human cancer cells impaired cell growth but had no detectable effect on telomere length, although hRif1 overexpression in S. cerevisiae interfered with telomere length control, in a manner specifically dependent on the presence of yeast Rif1 p. No localization of hRif1 on normal human telomeres, or interaction with the human telomeric proteins TRF1, TRF2, or hRap1, was detectable. However, hRif1 efficiently translocated to telomerically located DNA damage foci in response to the synthesis of aberrant telomeres directed by mutant-template telomerase RNA. The hRif1 level rose during late S/G2 but hRif1 was not visible on chromosomes in metaphase and anaphase; however, notably, specifically during early anaphase, hRif1 aligned along a subset of the midzone microtubules between the separating chromosomes. In telophase, hRif1 localized to chromosomes, and in interphase, it was intranuclear. These results define a novel subcellular localization behavior for hRif1 during the cell cycle.

Original languageEnglish (US)
Pages (from-to)819-830
Number of pages12
JournalJournal of Cell Biology
Volume167
Issue number5
DOIs
StatePublished - Dec 5 2004

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Anaphase
Telomere
Microtubules
Chromosomes
Telomeric Repeat Binding Protein 2
Telomeric Repeat Binding Protein 1
Telophase
Saccharomycetales
Interphase
DNA-Binding Proteins
Metaphase
RNA Interference
DNA Damage
Saccharomyces cerevisiae
Cell Cycle
Yeasts
Human Rif1 protein
Growth
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules. / Xu, Lifeng; Blackburn, Elizabeth H.

In: Journal of Cell Biology, Vol. 167, No. 5, 05.12.2004, p. 819-830.

Research output: Contribution to journalArticle

Xu, Lifeng ; Blackburn, Elizabeth H. / Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules. In: Journal of Cell Biology. 2004 ; Vol. 167, No. 5. pp. 819-830.
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