# Centromere
The **centromere** is the region of a chromosome that directs its segregation during mitosis and meiosis, the two forms of cell division that distribute genetic material to daughter cells and gametes[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/). It does so by recruiting the kinetochore, a large protein complex that attaches the chromosome to the microtubules of the mitotic spindle and acts as a signaling hub to ensure accurate chromosome segregation[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/). Although its functional importance has been appreciated for over 130 years, the molecular features that endow centromeres with this capacity remained a central challenge well into the 21st century[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/).
| Key fact | Detail |
|---|---|
| Core function | Directs chromosome segregation in mitosis and meiosis by recruiting the kinetochore, the structure that binds spindle microtubules[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/) |
| Epigenetic mark | The histone H3 variant CENP-A (CenH3) specifies centromere identity in most eukaryotes; specific DNA sequences are neither strictly necessary nor sufficient for centromere function[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/) |
| Structural types | Monocentric chromosomes carry point centromeres (short defined sequences, as in budding yeast) or regional centromeres (kilobases to megabases of DNA); [holocentric chromosomes](https://www.edgepedia.org/holocentric-chromosome) assemble a diffuse centromere along the whole chromosome[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/) |
| Human centromere DNA | Regional centromeres built on tandem α-satellite DNA arrays spanning 0.3–5 Mb, organized into chromosome-specific higher-order repeat (HOR) units[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC13470871/) |
| CENP-A nucleosome | Octameric, with two CENP-A molecules replacing H3; wraps 110–150 bp of DNA versus 147 bp for a canonical H3 nucleosome[3](https://link.springer.com/article/10.1007/s10577-025-09779-x) |
| Propagation | New CENP-A is deposited at exit from mitosis by the chaperone HJURP after PLK1-dependent activation of the Mis18 complex; replication dilutes CENP-A by 50% at each centromere[3](https://link.springer.com/article/10.1007/s10577-025-09779-x) |
| Sequence evolution | Human α-satellite HOR arrays mutate at a mean of about 4.07 × 10−7 mutations per base pair per generation, with a more than 20-fold range across chromosomes[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC13508068/) |
## Function in chromosome segregation
Faithful segregation requires each chromosome's centromere to build a kinetochore, a structure containing at least 100 different proteins that serves as the microtubule-binding site for the mitotic spindle[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC3687001/). The centromere is not a passive landing pad: the underlying chromatin itself dictates, in part, the geometry and function of the kinetochore and the mitotic spindle[6](https://pmc.ncbi.nlm.nih.gov/articles/PMC3288958/).
Kinetochores assemble and function specifically in mitosis, whereas centromeric chromatin and a group of centromere-binding proteins called the constitutive centromere-associated network (CCAN) are present throughout the cell cycle[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC3687001/). The CCAN, described in recent work as a complex of 16 centromeric proteins, forms the inner kinetochore and is essential for kinetochore assembly and mitotic fidelity[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
Kinetochores are molecular machines that power chromosome segregation during the mitotic and meiotic divisions of all eukaryotes[7](https://www.annualreviews.org/content/journals/10.1146/annurev-genet-072820-034559).
## Three functions beyond attachment
The main function of the centromere is to promote kinetochore assembly for spindle microtubule attachment, but two additional functions have become clear: facilitation of robust sister-chromatid cohesion at pericentromeres, the regions flanking the centromere, and advancement of replication of centromeric regions[8](https://link.springer.com/article/10.1038/embor.2013.181). The combination of these three functions ensures correct chromosome segregation during mitosis[8](https://link.springer.com/article/10.1038/embor.2013.181).
## Epigenetic identity
The defining feature of most eukaryotic centromeres is the presence of nucleosomes containing the histone H3 variant CENP-A, which specifies the centromere epigenetically[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/). In the majority of eukaryotes analyzed, specific DNA sequences are neither strictly necessary nor sufficient for centromere function; instead, propagation of chromatin-assembled CENP-A nucleosomes allows centromere identity to be inherited independently of the underlying DNA sequence[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5693723/).
Several lines of evidence support this epigenetic definition. A 1993 karyotyping study described a human chromosome fragment that had lost its centromeric DNA yet was stably maintained in mitosis, assembled a functional kinetochore, and mediated sister chromatid cohesion[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/). Neocentromeres, centromeres that emerge at new chromosomal locations lacking α-satellite DNA, show that identity is not dictated by DNA sequence[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). Conversely, artificially tethering CENP-A or its chaperone HJURP to non-centromeric chromatin is sufficient to form functional centromeres in flies and human cells, recruiting other kinetochore proteins such as CENP-C[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5693723/).
The CENP-A nucleosome itself has distinctive properties. After debate over several proposed compositions, studies converged on an octameric nucleosome containing two CENP-A molecules paired with H4, H2A, and H2B[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). Its DNA ends are flexibly unwound, mediated by CENP-A's shorter N-terminal tail and its CENP-A Targeting Domain, so it wraps 110–150 bp of DNA compared with 147 bp for an H3 nucleosome[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). This feature is thought to be important for binding of the CCAN[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
## Centromere DNA structure
Most eukaryotes have monocentric chromosomes, with the centromere assembled at a single localized region[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/). These fall into two classes. Point centromeres, found in some budding yeasts including *Saccharomyces cerevisiae*, are defined by a precise DNA sequence that is necessary and sufficient for kinetochore assembly: a 125 bp sequence divided into three conserved elements (CDE I, CDE II, and CDE III), with CENP-A (Cse4) deposited at the AT-rich CDE II region[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5693723/) • [3](https://link.springer.com/article/10.1007/s10577-025-09779-x). Regional centromeres, typical of most eukaryotes including humans, contain kilobases to megabases of repetitive DNA that contributes to, but is not sufficient for, centromere function[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/).
A notable exception is holocentricity, in which a diffuse centromere is assembled along the entire chromosome length; it occurs in some nematodes including *Caenorhabditis elegans*, some insects, and some plants[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/). Holocentric chromosomes lack a primary constriction because kinetochore activity extends along almost the entire chromosome during mitosis[10](https://pubmed.ncbi.nlm.nih.gov/27530342/).
Human centromeres are regional centromeres assembled on a portion of highly repetitive, tandem α-satellite DNA arrays spanning 0.3–5 Mb[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC13470871/). α-satellite DNA consists of 171 bp monomers organized into higher-order repeat (HOR) units present in hundreds to thousands of copies, with each chromosome carrying a unique HOR pattern[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC13470871/) • [3](https://link.springer.com/article/10.1007/s10577-025-09779-x). Some α-satellite monomers contain a 17 bp motif called the CENP-B box, which binds the CENP-B protein, the only centromeric protein known to recognize a specific centromeric DNA sequence[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). In humans, CENP-B boxes are found on all autosomes and the [X chromosome](https://www.edgepedia.org/x-chromosome) but are absent from the [Y chromosome](https://www.edgepedia.org/y-chromosome)[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
## Propagation through the cell cycle and the germline
CENP-A must be inherited with each chromosome through every cell cycle[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC5693723/). During [DNA replication](https://www.edgepedia.org/dna-replication), CENP-A is distributed to the two daughter centromeres, producing a 50% dilution at each centromere[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). New CENP-A deposition occurs at exit from mitosis through a stepwise process: PLK1-dependent phosphorylation activates the Mis18 complex, which licenses deposition of CENP-A by its chaperone HJURP[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). During replication itself, CENP-A reassembly onto daughter centromeres involves interactions with HJURP and MCM2 and requires CENP-C and the CCAN[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). The passage of the replication machinery strips CENP-A from ectopic sites on chromosome arms, restricting it to centromeres and reinforcing epigenetic identity[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
Centromeric chromatin is also remarkably stable through the germline. In mouse oocytes, CENP-A incorporated before prophase I arrest remains stable and functional for over a year, marking centromeres throughout oocyte development[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
## Sequence evolution and the centromere paradox
Centromere function is conserved over vast evolutionary time, yet the underlying centromeric repeat sequences evolve rapidly, a phenomenon known as the "centromere paradox"[11](https://www.sciencedirect.com/science/article/pii/S0014482720303748). Comparative analyses show that centromeric satellite DNA evolves through insertions, deletions, and gene conversion, driving high sequence divergence within and between species[3](https://link.springer.com/article/10.1007/s10577-025-09779-x). Despite this rapid evolution, some features of α-satellite sequences are maintained, including their repetitive and AT-rich character and, in many species, the CENP-B box, indicating selective pressure to preserve these properties while the exact nucleotide sequence may not be critical[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
Recent population-scale sequencing has quantified this variation. A study assembling 2,110 complete centromeres from 65 individuals representing 28 population groups, validated against a broader set totaling 8,340 centromeres, found that α-satellite HOR arrays mutate substantially faster than flanking unique sequence, at a mean of about 4.07 × 10−7 mutations per base pair per generation, and that centromeres exhibit a more than 20-fold range of mutation rates across chromosomes[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC13508068/). Within individuals, ddPCR measurements of five centromeric HOR arrays found up to tenfold variation in the length of the same array and up to 50-fold variation across different arrays between people from China, the UK, and the US[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
## The telomere-to-telomere era
Centromeres were long the last frontier of genome assemblies because short-read sequencing could not resolve long arrays of near-identical tandem repeats[11](https://www.sciencedirect.com/science/article/pii/S0014482720303748). A major milestone was the completion of the first fully assembled human genome, CHM13, by the Telomere-to-Telomere (T2T) [Consortium](https://www.edgepedia.org/consortium) in 2022, which used PacBio high-fidelity and Oxford Nanopore ultra-long sequencing to produce the first gapless assemblies of all repetitive sequences, including centromeric regions[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC13470871/). These assemblies revealed remarkable heterogeneity between chromosomes and genomes in the length, sequence, and position of the CENP-A domain[12](https://www.hubrecht.eu/app/uploads/2024/07/Kops_2024_Chromosoma.pdf), and showed that centromeric DNA evolves through layered expansions in which newer α-satellite variants arise and expand while older sequences shrink and diverge[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
The number of CENP-A nucleosomes marking a human centromere varies between centromeres and cell lines, ranging from about 50 to 300[12](https://www.hubrecht.eu/app/uploads/2024/07/Kops_2024_Chromosoma.pdf). CENP-A positioning is also dynamic over evolutionary timescales: centromere drift, the sliding of CENP-A nucleosomes within a genomic region, has now been observed in fission yeast, chicken, horse, and humans, with heterochromatin marks implicated in constraining drift and domain size[3](https://link.springer.com/article/10.1007/s10577-025-09779-x).
## References
1. [The molecular basis for centromere identity and function, Nature Reviews Molecular Cell Biology (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC8603311/)
2. [A genomic and epigenomic view of human centromeres, Nature Reviews Genetics (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC13470871/)
3. [The dynamic centromere, Chromosome Research (2025)](https://link.springer.com/article/10.1007/s10577-025-09779-x)
4. [A global view of human centromere variation and evolution (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC13508068/)
5. [Functions of the centromere and kinetochore in chromosome segregation (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3687001/)
6. [Centromeres: unique chromatin structures that drive chromosome segregation (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC3288958/)
7. [The Four Causes: The Functional Architecture of Centromeres and Kinetochores, Annual Review of Genetics (2022)](https://www.annualreviews.org/content/journals/10.1146/annurev-genet-072820-034559)
8. [Three wise centromere functions: see no error, hear no break, speak no delay, EMBO Reports (2013)](https://link.springer.com/article/10.1038/embor.2013.181)
9. [Centromere inheritance through the germline (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5693723/)
10. [Holocentromere identity: from the typical mitotic linear structure to the great plasticity of meiotic holocentromeres, PubMed](https://pubmed.ncbi.nlm.nih.gov/27530342/)
11. [Centromere studies in the era of 'telomere-to-telomere' genomics, Experimental Cell Research](https://www.sciencedirect.com/science/article/pii/S0014482720303748)
12. [Vertebrate centromere architecture: from chromatin threads to functional structures, Chromosoma (2024)](https://www.hubrecht.eu/app/uploads/2024/07/Kops_2024_Chromosoma.pdf)
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*Topic: Encyclopedia › Life and health › Biological foundations › Genetics and genomic reference › Chromosomes and cytogenetics*
*Initially written Sep 17, 2026 · Reviewed: Sep 30, 2026; Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license