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An H2A Histone Isotype, H2ac, Associates with Telomere and Maintains Telomere Integrity
- Source :
- PLoS ONE, Vol 11, Iss 5, p e0156378 (2016), PLoS ONE
- Publication Year :
- 2016
- Publisher :
- Public Library of Science (PLoS), 2016.
-
Abstract
- Telomeres are capped at the ends of eukaryotic chromosomes and are composed of TTAGGG repeats bound to the shelterin complex. Here we report that a replication-dependent histone H2A isotype, H2ac, was associated with telomeres in human cells and co-immunoprecipitates with telomere repeat factor 2 (TRF2) and protection of telomeres protein 1 (POT1), whereas other histone H2A isotypes and mutations of H2ac did not bind to telomeres or these two proteins. The amino terminal basic domain of TRF2 was necessary for the association with H2ac and for the recruitment of H2ac to telomeres. Depletion of H2ac led to loss of telomeric repeat sequences, the appearance of dysfunctional telomeres, and chromosomal instability, including chromosomal breaks and anaphase bridges, as well as accumulation of telomere-associated DNA damage factors in H2ac depleted cells. Additionally, knockdown of H2ac elicits an ATM-dependent DNA damage response at telomeres and depletion of XPF protects telomeres against H2ac-deficiency-induced G-strand overhangs loss and DNA damage response, and prevents chromosomal instability. These findings suggest that the H2A isotype, H2ac, plays an essential role in maintaining telomere functional integrity.
- Subjects :
- 0301 basic medicine
Telomerase
lcsh:Medicine
Ataxia Telangiectasia Mutated Proteins
Biochemistry
Shelterin Complex
Histones
0302 clinical medicine
Chromosome instability
Protein Isoforms
Telomeric Repeat Binding Protein 2
Small interfering RNAs
lcsh:Science
Telomere-binding protein
Multidisciplinary
biology
Chromosome Biology
Genomics
Telomere
Precipitation Techniques
Nucleic acids
Telomeres
Histone
030220 oncology & carcinogenesis
MCF-7 Cells
Research Article
Chromosome Structure and Function
DNA damage
Telomere-Binding Proteins
Molecular Probe Techniques
Research and Analysis Methods
Chromosomes
03 medical and health sciences
Telomere Homeostasis
Chromosomal Instability
DNA-binding proteins
Histone H2A
Genetics
Humans
Immunoprecipitation
Repeated Sequences
Non-coding RNA
Molecular Biology Techniques
Molecular Biology
lcsh:R
Biology and Life Sciences
Proteins
Cell Biology
DNA
Molecular biology
Probe Hybridization
Co-Immunoprecipitation
Gene regulation
030104 developmental biology
biology.protein
RNA
lcsh:Q
Gene expression
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....bda31961a65db0bed3f4b4a00890cbfa