Journal article
Human Flap Endonuclease I Is in Complex with Telomerase and Is Required for Telomerase-mediated Telomere Maintenance
The Journal of biological chemistry, Vol.284(6), pp.3682-3690
02/06/2009
Handle:
https://hdl.handle.net/2376/105469
PMCID: PMC2635043
PMID: 19068479
Abstract
Studies from budding yeast and ciliates have suggested that telomerase
extension of telomeres requires the conventional DNA replication machinery,
yet little is known about how DNA replication proteins regulate telomerase
action in higher eukaryotic cells. Here we investigate the role of one of the
DNA replication factors, flap endonuclease I (FEN1), in regulating telomerase
activity in mammalian cells. FEN1 is a nuclease that plays an important role
in DNA replication, repair, and recombination. We show that FEN1 is in complex
with telomerase
in vivo
via telomeric DNA. We further demonstrate
that FEN1 deficiency in mouse embryonic fibroblasts leads to an increase in
telomere end-to-end fusions. In cancer cells, FEN1 deficiency induces gradual
shortening of telomeres but does not alter the single-stranded G-overhangs.
This is, to our knowledge, the first evidence that FEN1 and telomerase
physically co-exist as a complex and that FEN1 can regulate telomerase
activity at telomeres in mammalian cells.
Metrics
10 Record Views
Details
- Title
- Human Flap Endonuclease I Is in Complex with Telomerase and Is Required for Telomerase-mediated Telomere Maintenance
- Creators
- Shilpa Sampathi - Washington, Wyoming, Alaska, Montana, Idaho Medical Education Program and School of Molecular Biosciences, Washington State University, Spokane, Washington 99210, theAmruta Bhusari - Washington, Wyoming, Alaska, Montana, Idaho Medical Education Program and School of Molecular Biosciences, Washington State University, Spokane, Washington 99210, theBinghui Shen - Washington, Wyoming, Alaska, Montana, Idaho Medical Education Program and School of Molecular Biosciences, Washington State University, Spokane, Washington 99210, theWeihang Chai - Washington, Wyoming, Alaska, Montana, Idaho Medical Education Program and School of Molecular Biosciences, Washington State University, Spokane, Washington 99210, the
- Publication Details
- The Journal of biological chemistry, Vol.284(6), pp.3682-3690
- Academic Unit
- UNKNOWN
- Publisher
- American Society for Biochemistry and Molecular Biology
- Identifiers
- 99900546875601842
- Language
- English
- Resource Type
- Journal article