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Centromere protein A, also known as CENPA, is a protein which in humans is encoded by the CENPAgene.[5]
Function
Centromeres are the chromosomal domains that specify the mitotic behavior of chromosomes. The CENPA gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. CENPA is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[5]
In higher eukaryotes, the recruitment of CENP-A nucleosomes to existing centromeres is an epigenetic process, independent of the underlying DNA sequence. In S.pombe, de novo recruitment of the CENP-A to the centromere is believed to be controlled by "centromeric" heterochromatin surrounding the centromere, and by an RNAi mechanism. The RNAi is cut to form siRNA; this complexes with the protein Chp1, which then binds the centromeric heterochromatin. This helps recruit other proteins, ultimately resulting in a protein complex that forms cohesin between two sister chromatids at the centromeric heterochromatin. This cohesin is believed to be essential in replacing the centromere H3 with CENP-A. CENP-A is one of the epigenetic changes that is believed to distinguish centromeric DNA from other DNA.[6] Once the CENP-A has been added, the centromere becomes self-propagating, and the surrounding heterochromatin/RNAi mechanism is no longer necessary.[7]
^Chueh AC, Wong LH, Wong N, Choo KH (January 2005). "Variable and hierarchical size distribution of L1-retroelement-enriched CENP-A clusters within a functional human neocentromere". Hum. Mol. Genet. 14 (1): 85–93. doi:10.1093/hmg/ddi008. PMID15537667.
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Lomonte P, Sullivan KF, Everett RD (2001). "Degradation of nucleosome-associated centromeric histone H3-like protein CENP-A induced by herpes simplex virus type 1 protein ICP0". J. Biol. Chem. 276 (8): 5829–35. doi:10.1074/jbc.M008547200. PMID11053442.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH (2001). "Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype". Curr. Biol. 10 (21): 1319–28. doi:10.1016/S0960-9822(00)00769-7. PMID11084331.
Saxena A, Saffery R, Wong LH, Kalitsis P, Choo KH (2002). "Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated". J. Biol. Chem. 277 (30): 26921–6. doi:10.1074/jbc.M200620200. PMID12011073.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Saxena A, Wong LH, Kalitsis P, Earle E, Shaffer LG, Choo KH (2003). "Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc". Hum. Mol. Genet. 11 (19): 2319–29. doi:10.1093/hmg/11.19.2319. PMID12217960.
Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T, Shimada H, Ochiai T, Yoda K, Nomura F (2003). "Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer". Cancer Res. 63 (13): 3511–6. PMID12839935.
Kunitoku N, Sasayama T, Marumoto T, Zhang D, Honda S, Kobayashi O, Hatakeyama K, Ushio Y, Saya H, Hirota T (2004). "CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function". Dev. Cell. 5 (6): 853–64. doi:10.1016/S1534-5807(03)00364-2. PMID14667408.
Obuse C, Yang H, Nozaki N, Goto S, Okazaki T, Yoda K (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 Cells. 9 (2): 105–20. doi:10.1111/j.1365-2443.2004.00705.x. PMID15009096.
Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S (2004). "Cdc42 and mDia3 regulate microtubule attachment to kinetochores". Nature. 428 (6984): 767–71. doi:10.1038/nature02452. PMID15085137.
Black BE, Foltz DR, Chakravarthy S, Luger K, Woods VL Jr, Cleveland DW (2004). "Structural determinants for generating centromeric chromatin". Nature. 430 (6999): 578–82. doi:10.1038/nature02766. PMID15282608.
