Publications | A complex comprising C15ORF41 and Codanin-1- the products of two genes mutated in congenital dyserythropoietic anemia type I (CDA-I).

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 characterization 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. These findings in this study have major implications for the understanding of C15ORF41 and Codanin-1 function and CDA-I.

Principal Investigator(s):

Author(s):
Shroff M, Knebel A, Toth R, Rouse J.

PubMed:
32239177
Citation:
Shroff M, Knebel A, Toth R, Rouse J.
Biochem J
2020
ii: BCJ20190944. doi: 10.1042/BCJ20190944
PMID: 32239177