Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S-phase histone supply
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Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S-phase histone supply. / Ask, Katrine; Jasencakova, Zusana; Menard, Patrice; Feng, Yunpeng; Almouzni, Geneviève; Groth, Anja.
In: E M B O Journal, Vol. 31, No. 8, 2012, p. 2013-23.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Codanin-1, mutated in the anaemic disease CDAI, regulates Asf1 function in S-phase histone supply
AU - Ask, Katrine
AU - Jasencakova, Zusana
AU - Menard, Patrice
AU - Feng, Yunpeng
AU - Almouzni, Geneviève
AU - Groth, Anja
PY - 2012
Y1 - 2012
N2 - Efficient supply of new histones during DNA replication is critical to restore chromatin organization and maintain genome function. The histone chaperone anti-silencing function 1 (Asf1) serves a key function in providing H3.1-H4 to CAF-1 for replication-coupled nucleosome assembly. We identify Codanin-1 as a novel interaction partner of Asf1 regulating S-phase histone supply. Mutations in Codanin-1 can cause congenital dyserythropoietic anaemia type I (CDAI), characterized by chromatin abnormalities in bone marrow erythroblasts. Codanin-1 is part of a cytosolic Asf1-H3.1-H4-Importin-4 complex and binds directly to Asf1 via a conserved B-domain, implying a mutually exclusive interaction with the chaperones CAF-1 and HIRA. Codanin-1 depletion accelerates the rate of DNA replication and increases the level of chromatin-bound Asf1, suggesting that Codanin-1 guards a limiting step in chromatin replication. Consistently, ectopic Codanin-1 expression arrests S-phase progression by sequestering Asf1 in the cytoplasm, blocking histone delivery. We propose that Codanin-1 acts as a negative regulator of Asf1 function in chromatin assembly. This function is compromised by two CDAI mutations that impair complex formation with Asf1, providing insight into the molecular basis for CDAI disease.
AB - Efficient supply of new histones during DNA replication is critical to restore chromatin organization and maintain genome function. The histone chaperone anti-silencing function 1 (Asf1) serves a key function in providing H3.1-H4 to CAF-1 for replication-coupled nucleosome assembly. We identify Codanin-1 as a novel interaction partner of Asf1 regulating S-phase histone supply. Mutations in Codanin-1 can cause congenital dyserythropoietic anaemia type I (CDAI), characterized by chromatin abnormalities in bone marrow erythroblasts. Codanin-1 is part of a cytosolic Asf1-H3.1-H4-Importin-4 complex and binds directly to Asf1 via a conserved B-domain, implying a mutually exclusive interaction with the chaperones CAF-1 and HIRA. Codanin-1 depletion accelerates the rate of DNA replication and increases the level of chromatin-bound Asf1, suggesting that Codanin-1 guards a limiting step in chromatin replication. Consistently, ectopic Codanin-1 expression arrests S-phase progression by sequestering Asf1 in the cytoplasm, blocking histone delivery. We propose that Codanin-1 acts as a negative regulator of Asf1 function in chromatin assembly. This function is compromised by two CDAI mutations that impair complex formation with Asf1, providing insight into the molecular basis for CDAI disease.
KW - Amino Acid Sequence
KW - Anemia, Dyserythropoietic, Congenital
KW - Cell Cycle Proteins
KW - Chromosomes
KW - DNA Replication
KW - Glycoproteins
KW - HeLa Cells
KW - Histones
KW - Humans
KW - Models, Biological
KW - Molecular Sequence Data
KW - Mutant Proteins
KW - Mutation, Missense
KW - Protein Binding
KW - Protein Interaction Mapping
KW - S Phase
U2 - 10.1038/emboj.2012.55
DO - 10.1038/emboj.2012.55
M3 - Journal article
C2 - 22407294
VL - 31
SP - 2013
EP - 2023
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 8
ER -
ID: 38308791