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CENPA a genomic marker for centromere activity and human diseases. | LitMetric

CENPA a genomic marker for centromere activity and human diseases.

Curr Genomics

Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Cádiz, 11510 Puerto Real, Cádiz, Spain.

Published: August 2009

AI Article Synopsis

Article Abstract

Inheritance of genetic material requires that chromosomes segregate faithfully during cell division. Failure in this process can drive to aneuploidy phenomenon. Kinetochores are unique centromere macromolecular protein structures that attach chromosomes to the spindle for a proper movement and segregation. A unique type of nucleosomes of centromeric chromatin provides the base for kinetochore formation. A specific histone H3 variant, CENPA, replaces conventional histone H3 and together with centromere-specific-DNA-binding factors directs the assembly of active kinetochores. Recent studies on CENPA nucleosomal structure, epigenetic inheritance of centromeric chromatin and transcription of pericentric heterochromatin provide new clues to our understanding of centromere structure and function. This review highlights the role and dynamics of CENPA assembly into centromeres and the potential contribution of this kinetochore protein to autoimmune and cancer diseases in humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729997PMC
http://dx.doi.org/10.2174/138920209788920985DOI Listing

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In eukaryotes, accurate chromosome segregation during cell division relies on the centromeric histone H3 variant, CENH3. Our previous work identified KINETOCHORE NULL2 (αKNL2) as a plant CENH3 assembly factor, which contains a centromere-targeting motif, CENPC-k, analogous to the CENPC motif found in CENP-C. We also demonstrated that αKNL2 can bind DNA in vitro in a sequence-independent manner, without the involvement of its CENPC-k motif.

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Background: Organization of the eukaryotic genome is essential for proper function, including gene expression. In metazoans, chromatin loops and Topologically Associated Domains (TADs) organize genes into transcription factories, while chromosomes occupy nuclear territories in which silent heterochromatin is compartmentalized at the nuclear periphery and active euchromatin localizes to the nucleus center. A similar hierarchical organization occurs in the fungus Neurospora crassa where its seven chromosomes form a Rabl conformation typified by heterochromatic centromeres and telomeres independently clustering at the nuclear membrane, while interspersed heterochromatic loci aggregate across Megabases of linear genomic distance to loop chromatin in TAD-like structures.

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The mammalian kinetochore is a multi-layered protein complex that forms on the centromeric chromatin. The kinetochore serves as the attachment hub for the plus ends of microtubules emanating from the centrosomes during mitosis. For karyokinesis, bipolar kinetochore-microtubule attachment and subsequent microtubule depolymerization lead to the development of inter-kinetochore tension between the sister chromatids.

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Motivation: Centromeres are chromosomal regions historically understudied with sequencing technologies due to their repetitive nature and short-read mapping limitations. However, recent improvements in long-read sequencing allow for the investigation of complex regions of the genome at the sequence and epigenetic levels.

Results: Here, we present Centromere Dip Region (CDR)-Finder: a tool to identify regions of hypomethylation within the centromeres of high-quality, contiguous genome assemblies.

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KDM1A-mediated ZFP64 demethylation activates CENPL to promote epithelial ovarian cancer progression.

Cytotechnology

February 2025

Department of Oncology, Gaochun People's Hospital Affiliated to Jiangsu Health Vocational College, No. 53, Maoshan Road, Gaochun Economic Development Zone, Nanjing, 211306 Jiangsu People's Republic of China.

Article Synopsis
  • KDM1A is overexpressed in epithelial ovarian cancer (EOC) and plays a significant role in promoting malignant behaviors of EOC cells.
  • The study utilized various assays and mouse models to investigate the effects of KDM1A, ZFP64, and CENPL on EOC cell functions and found that knocking down these proteins inhibited EOC cell behavior.
  • The research concluded that KDM1A enhances EOC progression through the activation of the ZFP64/CENPL pathway, promoting cell proliferation, migration, and invasion while reducing apoptosis.
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