From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Centromere protein A , also known as CENPA , is a
protein which in humans is encoded by the CENPA
gene .
[5] CENPA is a
histone H3
variant which is the critical factor determining the
kinetochore
position(s) on each
chromosome
[6] in most
eukaryotes including humans.
Function CENPA is a protein which
epigenetically defines the position of the centromere on each chromosome,
[7] determining the position of kinetochore assembly and the final site of
sister chromatid cohesion during
mitosis . This proteins is frequently accompanied by "centrochromatin"-associated changes to canonical histones and is constitutively present in centromeres.
[8] The CENPA protein is a histone H3 variant which replaces one or both
canonical H3 histones in a subset of
nucleosomes within centromeric
chromatin .
[9]
[10] CENPA has the greatest sequence divergence of the histone H3 variants, with just 48% similarity to canonical histone H3, and has a highly diverged
N-terminal tail that lacks many well characterised
histone modification sites including H3K4, H3K9 and H3K27.
[11]
Unusually for a histone, CENPA nucleosomes are not
loaded together with
DNA replication and are loaded at different
cell cycle stages in different organisms:
G1 phase in human,
[12]
M phase in drosophila,
[13]
G2 in S. pombe.
[14] To orchestrate this specialised loading there are CENPA-specific histone
chaperones :
HJURP in human, CAL1 in
drosophila and Scm3 in
S. pombe .
[15] In most eukaryotes CENPA is loaded into large domains of highly
repetitive satellite DNA .
[16] The position of CENPA within satellite DNA are
heritable at the protein level through a purely epigenetic mechanism.
[17] This means that the position of CENPA protein binding to the genome is copied upon
cell division to the two daughter cells independent of the underlying DNA sequence. Under circumstances in which CENPA is lost from a chromosome a
fail-safe mechanism has been described in human cells in which
CENPB recruits CENPA via a satellite
DNA binding domain to repopulate the centromere with CENPA nucleosomes.
[18]
CENPA interacts directly with the
inner kinetochore through proteins including
CENPC and
CENPN .
[19]
[20] Through this interaction the
microtubules are able to accurately
segregate chromosomes during mitosis.
References
^
a b c
GRCh38: Ensembl release 89: ENSG00000115163 –
Ensembl , May 2017
^
a b c
GRCm38: Ensembl release 89: ENSMUSG00000029177 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
EntrezGene
1058
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^ Gurard-Levin ZA, Quivy JP, Almouzni G (2014). "Histone chaperones: assisting histone traffic and nucleosome dynamics". Annual Review of Biochemistry . 83 : 487–517.
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^ Plohl M, Meštrović N, Mravinac B (August 2014).
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^ Aldrup-MacDonald ME, Kuo ME, Sullivan LL, Chew K, Sullivan BA (October 2016).
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^ van den Berg SJ, Jansen LE (October 2020).
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^ Kixmoeller K, Allu PK, Black BE (June 2020).
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External links Further reading
Palmer DK, O'Day K, Trong HL, Charbonneau H, Margolis RL (May 1991).
"Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone" . Proceedings of the National Academy of Sciences of the United States of America . 88 (9): 3734–3738.
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10.1073/pnas.88.9.3734 .
PMC
51527 .
PMID
2023923 . Sullivan KF, Hechenberger M, Masri K (November 1994).
"Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere" . The Journal of Cell Biology . 127 (3): 581–592.
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PMC
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PMID
7962047 . Shelby RD, Vafa O, Sullivan KF (February 1997).
"Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites" . The Journal of Cell Biology . 136 (3): 501–513.
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PMC
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PMID
9024683 . Valdivia MM, Figueroa J, Iglesias C, Ortíz M (January 1998).
"A novel centromere monospecific serum to a human autoepitope on the histone H3-like protein CENP-A" . FEBS Letters . 422 (1): 5–9.
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S2CID
40104381 . Fowler KJ, Newson AJ, MacDonald AC, Kalitsis P, Lyu MS, Kozak CA, et al. (1998). "Chromosomal localization of mouse Cenpa gene". Cytogenetics and Cell Genetics . 79 (3–4): 298–301.
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PMID
9605877 . Muro Y, Azuma N, Onouchi H, Kunimatsu M, Tomita Y, Sasaki M, et al. (April 2000).
"Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3" . Clinical and Experimental Immunology . 120 (1): 218–223.
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PMC
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PMID
10759786 . Lomonte P, Sullivan KF, Everett RD (February 2001).
"Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0" . The Journal of Biological Chemistry . 276 (8): 5829–5835.
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PMID
11053442 . Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, et al. (November 2000).
"Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype" . Current Biology . 10 (21): 1319–1328.
Bibcode :
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doi :
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PMID
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S2CID
18455745 . Zeitlin SG, Shelby RD, Sullivan KF (December 2001).
"CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis" . The Journal of Cell Biology . 155 (7): 1147–1157.
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PMID
11756469 . Ando S, Yang H, Nozaki N, Okazaki T, Yoda K (April 2002).
"CENP-A, -B, and -C chromatin complex that contains the I-type alpha-satellite array constitutes the prekinetochore in HeLa cells" . Molecular and Cellular Biology . 22 (7): 2229–2241.
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PMID
11884609 . Saxena A, Saffery R, Wong LH, Kalitsis P, Choo KH (July 2002).
"Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated" . The Journal of Biological Chemistry . 277 (30): 26921–26926.
doi :
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PMID
12011073 . Figueroa J, Pendón C, Valdivia MM (May 2002).
"Molecular cloning and sequence analysis of hamster CENP-A cDNA" . BMC Genomics . 3 : 11.
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PMC
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PMID
12019018 . Saxena A, Wong LH, Kalitsis P, Earle E, Shaffer LG, Choo KH (September 2002).
"Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc" . Human Molecular Genetics . 11 (19): 2319–2329.
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PMID
12217960 . Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H, Ochiai T, et al. (July 2003). "Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer". Cancer Research . 63 (13): 3511–3516.
PMID
12839935 . Kunitoku N, Sasayama T, Marumoto T, Zhang D, Honda S, Kobayashi O, et al. (December 2003).
"CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function" . Developmental Cell . 5 (6): 853–864.
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PMID
14667408 . Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (February 2004).
"Proteomics analysis of the centromere complex from HeLa interphase cells: UV-damaged DNA binding protein 1 (DDB-1) is a component of the CEN-complex, while BMI-1 is transiently co-localized with the centromeric region in interphase" . Genes to Cells . 9 (2): 105–120.
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PMID
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S2CID
21813024 . Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, et al. (April 2004). "Cdc42 and mDia3 regulate microtubule attachment to kinetochores". Nature . 428 (6984): 767–771.
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2004Natur.428..767Y .
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S2CID
4401953 . Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL, Cleveland DW (July 2004). "Structural determinants for generating centromeric chromatin". Nature . 430 (6999): 578–582.
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2004Natur.430..578B .
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PMID
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S2CID
4392941 . Sullivan BA, Karpen GH (November 2004).
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PMC
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PMID
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"The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres" . Nature . 467 (7313): 347–351.
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Basic Types Processes Structures
See also
