CENPA

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Centromere protein A
Protein CENPA PDB 3NQJ.png
Rendering based on PDB 3NQJ.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CENPA ; CENP-A; CenH3
External IDs OMIM117139 MGI88375 HomoloGene1369 GeneCards: CENPA Gene
Orthologs
Species Human Mouse
Entrez 1058 12615
Ensembl ENSG00000115163 ENSMUSG00000029177
UniProt P49450 O35216
RefSeq (mRNA) NM_001042426 NM_007681
RefSeq (protein) NP_001035891 NP_031707
Location (UCSC) Chr 2:
26.99 – 27.02 Mb
Chr 5:
30.67 – 30.67 Mb
PubMed search [1] [2]

Centromere protein A, also known as CENPA, is a protein which in humans is encoded by the CENPA gene.[1]

Function[edit]

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.[1]

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.[2] Once the CENP-A has been added, the centromere becomes self-propagating, and the surrounding heterochromatin/RNAi mechanism is no longer necessary.[3]

References[edit]

  1. ^ a b EntrezGene 1058
  2. ^ 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. PMID 15537667. 
  3. ^ Folco HD, Pidoux AL, Urano T, Allshire RC (January 2008). "Heterochromatin and RNAi are required to establish CENP-A chromatin at centromeres". Science 319 (5859): 94–7. doi:10.1126/science.1150944. PMC 2586718. PMID 18174443. 

Further reading[edit]