A complex comprising C15ORF41 and Codanin-1: the products of two genes mutated in congenital dyserythropoietic anaemia type I (CDA-I).
Biochem J
; 477(10): 1893-1905, 2020 05 29.
Article
en En
| MEDLINE
| ID: mdl-32239177
ABSTRACT
Congenital dyserythropoietic anaemia (CDA) type I is a rare blood disorder characterised by moderate to severe macrocytic anaemia and hepatomegaly, with spongy heterochromatin and inter-nuclear bridges seen in bone marrow erythroblasts. The vast majority of cases of CDA type I are caused by mutations in the CDAN1 gene. The product of CDAN1 is Codanin-1, which interacts the histone chaperone ASF1 in the cytoplasm. Codanin-1 is a negative regulator of chromatin replication, sequestering ASF1 in the cytoplasm, restraining histone deposition and thereby limiting DNA replication. The remainder of CDA-I cases are caused by mutations in the C15ORF41 gene, but very little is known about the product of this gene. Here, we report that C15ORF41 forms a tight, near-stoichiometric complex with Codanin1 in human cells, interacting with the C-terminal region of Codanin-1. We present the characterisation of the C15ORF41-Codanin-1 complex in humans in cells and in vitro, and demonstrate that Codanin-1 appears to sequester C15ORF41 in the cytoplasm as previously shown for ASF1. The findings in this study have major implications for understanding the functions of C15ORF41 and Codanin-1, and the aetiology of CDA-I.
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Base de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
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Glicoproteínas
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Proteínas de Ciclo Celular
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Complejos Multiproteicos
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Anemia Diseritropoyética Congénita
Idioma:
En
Revista:
Biochem J
Año:
2020
Tipo del documento:
Article