ArticleProceedings of the National Academy of Sciences of the United States of America2017
Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79 citing papers in PubMed, 129 citations in OpenAlex.
- Article
- Determinants of centromeric nucleosome conformation.bioRxiv : the preprint server for biology · 2026Article
- Targeting FAM83D triggers tumor cell senescence via cGAS-STING signaling activation and reprograms TAMs to combat glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Impact of Tau overexpression on DNA replication dynamics in centromeres of human neural progenitor cells.iScience · 2026Article
- Pericentromeric Transcription of Novel Pathogen-Related Human GPS Genes in Cancers is Regulated by C19MC miRNAs, CEBPB, IFN-γ, and IFN-β.Research square · 2026Article
- Article
- 40 years of CENP-A: the foundation of a new era of centromere biology.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025Article
- Cell line-matched reference enables high-precision functional genomics.Nature communications · 2025Article
- Unveiling the regulatory potential of the non-coding genome: Insights from the human genome project to precision medicine.Genes & diseases · 2025Review
- The reference genome of the human diploid cell line RPE-1.Nature communications · 2025Article
- Centromeres drive and take a break.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025Review
- Total whole-arm chromosome losses predict malignancy in human cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fast sequence alignment for centromeres with RaMA.Genome research · 2025Article
- PBRM1 directs PBAF to pericentromeres and protects centromere integrity.Nature communications · 2025Article
- The homologous recombination factors BRCA2 and PALB2 interplay with mismatch repair pathways to maintain centromere stability and cell viability.Cell reports · 2025Article
- Centromere inactivation during aging can be rescued in human cells.Molecular cell · 2025Article
- Comparative analysis of predicted DNA secondary structures infers complex human centromere topology.American journal of human genetics · 2024Article
- DNA strand breaks at centromeres: Friend or foe?Seminars in cell & developmental biology · 2024Review
- Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets.Cell death discovery · 2024Review
- Tigerfish designs oligonucleotide-based in situ hybridization probes targeting intervals of highly repetitive DNA at the scale of genomes.Nature communications · 2024Article
19 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Centromeres are highly specialized chromatin domains that enable chromosome segregation and orchestrate faithful cell division. Human centromeres are composed of tandem arrays of α-satellite DNA, which spans up to several megabases. Little is known about the mechanisms that maintain integrity of the long arrays of α-satellite DNA repeats. Here, we monitored centromeric repeat stability in human cells using chromosome-orientation fluorescent in situ hybridization (CO-FISH). This assay detected aberrant centromeric CO-FISH patterns consistent with sister chromatid exchange at the frequency of 5% in primary tissue culture cells, whereas higher levels were seen in several cancer cell lines and during replicative senescence. To understand the mechanism(s) that maintains centromere integrity, we examined the contribution of the centromere-specific histone variant CENP-A and members of the constitutive centromere-associated network (CCAN), CENP-C, CENP-T, and CENP-W. Depletion of CENP-A and CCAN proteins led to an increase in centromere aberrations, whereas enhancing chromosome missegregation by alternative methods did not, suggesting that CENP-A and CCAN proteins help maintain centromere integrity independently of their role in chromosome segregation. Furthermore, superresolution imaging of centromeric CO-FISH using structured illumination microscopy implied that CENP-A protects α-satellite repeats from extensive rearrangements. Our study points toward the presence of a centromere-specific mechanism that actively maintains α-satellite repeat integrity during human cell proliferation.
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