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Protein-coding gene in the species Homo sapiens
Centromere protein A ,also known asCENPA ,is aprotein which in humans is encoded by theCENPA gene .[5] histone H3 variant which is the critical factor determining thekinetochore position(s) on eachchromosome [6] eukaryotes including humans.
Function [ edit ] CENPA is a protein whichepigenetically defines the position of the centromere on each chromosome,[7] sister chromatid cohesion duringmitosis .This proteins is frequently accompanied by "centrochromatin" -associated changes to canonical histones and is constitutively present in centromeres.[8] canonical H3 histones in a subset ofnucleosomes within centromericchromatin .[9] [10] N-terminal tail that lacks many well characterisedhistone modification sites including H3K4, H3K9 and H3K27.[11]
Unusually for a histone, CENPA nucleosomes are notloaded together withDNA replication and are loaded at differentcell cycle stages in different organisms:G1 phase in human,[12] M phase in drosophila,[13] G2 in S. pombe.[14] chaperones :HJURP in human, CAL1 indrosophila and Scm3 inS. pombe .[15] repetitive satellite DNA .[16] heritable at the protein level through a purely epigenetic mechanism.[17] cell division to the two daughter cells independent of the underlying DNA sequence. Under circumstances in which CENPA is lost from a chromosome afail-safe mechanism has been described in human cells in whichCENPB recruits CENPA via a satelliteDNA binding domain to repopulate the centromere with CENPA nucleosomes.[18]
CENPA interacts directly with theinner kinetochore through proteins includingCENPC andCENPN .[19] [20] microtubules are able to accuratelysegregate chromosomes during mitosis.
References [ edit ]
^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 ^ Allshire RC, Karpen GH (December 2008)."Epigenetic regulation of centromeric chromatin: old dogs, new tricks?" .Nature Reviews. Genetics .9 (12): 923–937.doi :10.1038/nrg2466 .PMC 2586333 PMID 19002142 . ^ Fachinetti D, Folco HD, Nechemia-Arbely Y, Valente LP, Nguyen K, Wong AJ, et al. (September 2013)."A two-step mechanism for epigenetic specification of centromere identity and function" .Nature Cell Biology .15 (9): 1056–1066.doi :10.1038/ncb2805 .PMC 4418506 PMID 23873148 . ^ Altemose N, Logsdon GA, Bzikadze AV, Sidhwani P, Langley SA, Caldas GV, et al. (April 2022)."Complete genomic and epigenetic maps of human centromeres" .Science .376 (6588): eabl4178.doi :10.1126/science.abl4178 .PMC 9233505 PMID 35357911 . ^ Blower MD, Sullivan BA, Karpen GH (March 2002)."Conserved organization of centromeric chromatin in flies and humans" .Developmental Cell .2 (3): 319–330.doi :10.1016/s1534-5807(02)00135-1 .PMC 3192492 PMID 11879637 . ^ Nechemia-Arbely Y, Fachinetti D, Miga KH, Sekulic N, Soni GV, Kim DH, et al. (March 2017)."Human centromeric CENP-A chromatin is a homotypic, octameric nucleosome at all cell cycle points" .The Journal of Cell Biology .216 (3): 607–621.doi :10.1083/jcb.201608083 .PMC 5350519 PMID 28235947 . ^ Srivastava S, Foltz DR (September 2018)."Posttranslational modifications of CENP-A: marks of distinction" .Chromosoma .127 (3): 279–290.doi :10.1007/s00412-018-0665-x .PMC 6082721 PMID 29569072 . ^ Jansen LE, Black BE, Foltz DR, Cleveland DW (March 2007)."Propagation of centromeric chromatin requires exit from mitosis" .The Journal of Cell Biology .176 (6): 795–805.doi :10.1083/jcb.200701066 .PMC 2064054 PMID 17339380 . ^ Schuh M, Lehner CF, Heidmann S (February 2007). "Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early embryonic anaphase".Current Biology .17 (3): 237–243.Bibcode :2007CBio...17..237S .doi :10.1016/j.cub.2006.11.051 .hdl :11858/00-001M-0000-002A-23E4-7 PMID 17222555 .S2CID 17907028 . ^ Shukla M, Tong P, White SA, Singh PP, Reid AM, Catania S, et al. (December 2018)."Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition during the Cell Cycle" .Current Biology .28 (24): 3924–3936.e4.Bibcode :2018CBio...28E3924S .doi :10.1016/j.cub.2018.10.049 .PMC 6303189 PMID 30503616 . ^ Gurard-Levin ZA, Quivy JP, Almouzni G (2014). "Histone chaperones: assisting histone traffic and nucleosome dynamics".Annual Review of Biochemistry .83 :487–517.doi :10.1146/annurev-biochem-060713-035536 .PMID 24905786 . ^ Plohl M, Meštrović N, Mravinac B (August 2014)."Centromere identity from the DNA point of view" .Chromosoma .123 (4): 313–325.doi :10.1007/s00412-014-0462-0 .PMC 4107277 PMID 24763964 . ^ Aldrup-MacDonald ME, Kuo ME, Sullivan LL, Chew K, Sullivan BA (October 2016)."Genomic variation within Alpha satellite DNA influences centromere location on human chromosomes with metastable epialleles" .Genome Research .26 (10): 1301–1311.doi :10.1101/gr.206706.116 .PMC 5052062 PMID 27510565 . ^ van den Berg SJ, Jansen LE (October 2020)."Centromeres: genetic input to calibrate an epigenetic feedback loop" .The EMBO Journal .39 (20): e106638.doi :10.15252/embj.2020106638 .PMC 7560195 PMID 32959893 . ^ Kixmoeller K, Allu PK, Black BE (June 2020)."The centromere comes into focus: from CENP-A nucleosomes to kinetochore connections with the spindle" .Open Biology .10 (6): 200051.doi :10.1098/rsob.200051 .PMC 7333888 PMID 32516549 . ^ Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, et al. (October 2019)."Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome" .Nature .574 (7777): 278–282.Bibcode :2019Natur.574..278Y .doi :10.1038/s41586-019-1609-1 .PMC 6859074 PMID 31578520 .
External links [ edit ] Further reading [ edit ]
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.Bibcode :1991PNAS...88.3734P .doi :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.doi :10.1083/jcb.127.3.581 .PMC 2120219 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.doi :10.1083/jcb.136.3.501 .PMC 2134286 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.doi :10.1016/S0014-5793(97)01583-4 PMID 9475158 .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.doi :10.1159/000134748 .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.doi :10.1046/j.1365-2249.2000.01189.x .PMC 1905620 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.doi :10.1074/jbc.M008547200 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 :2000CBio...10.1319U .doi :10.1016/S0960-9822(00)00769-7 PMID 11084331 .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.doi :10.1083/jcb.200108125 .PMC 2199334 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.doi :10.1128/MCB.22.7.2229-2241.2002 .PMC 133672 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 :10.1074/jbc.M200620200 PMID 12011073 . Figueroa J, Pendón C, Valdivia MM (May 2002)."Molecular cloning and sequence analysis of hamster CENP-A cDNA" .BMC Genomics .3 :11.doi :10.1186/1471-2164-3-11 PMC 113255 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.doi :10.1093/hmg/11.19.2319 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.doi :10.1016/S1534-5807(03)00364-2 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.doi :10.1111/j.1365-2443.2004.00705.x PMID 15009096 .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.Bibcode :2004Natur.428..767Y .doi :10.1038/nature02452 .PMID 15085137 .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.Bibcode :2004Natur.430..578B .doi :10.1038/nature02766 .PMID 15282608 .S2CID 4392941 . Sullivan BA, Karpen GH (November 2004)."Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin" .Nature Structural & Molecular Biology .11 (11): 1076–1083.doi :10.1038/nsmb845 .PMC 1283111 PMID 15475964 . Sekulic N, Bassett EA, Rogers DJ, Black BE (September 2010)."The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres" .Nature .467 (7313): 347–351.Bibcode :2010Natur.467..347S .doi :10.1038/nature09323 .PMC 2946842 PMID 20739937 .
Basic Types Processes Structures
See also
