Mrc1 regulates parental histone segregation and heterochromatin inheritance.
Mol Cell
; 84(17): 3223-3236.e4, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-39094566
ABSTRACT
Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Schizosaccharomyces
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Heterocromatina
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Histonas
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Proteínas de Schizosaccharomyces pombe
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Epigênese Genética
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Replicação do DNA
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos