The fork protection complex promotes parental histone recycling and epigenetic memory.
Cell
; 187(18): 5029-5047.e21, 2024 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-39094569
ABSTRACT
The inheritance of parental histones across the replication fork is thought to mediate epigenetic memory. Here, we reveal that fission yeast Mrc1 (CLASPIN in humans) binds H3-H4 tetramers and operates as a central coordinator of symmetric parental histone inheritance. Mrc1 mutants in a key connector domain disrupted segregation of parental histones to the lagging strand comparable to Mcm2 histone-binding mutants. Both mutants showed clonal and asymmetric loss of H3K9me-mediated gene silencing. AlphaFold predicted co-chaperoning of H3-H4 tetramers by Mrc1 and Mcm2, with the Mrc1 connector domain bridging histone and Mcm2 binding. Biochemical and functional analysis validated this model and revealed a duality in Mrc1 function disabling histone binding in the connector domain disrupted lagging-strand recycling while another histone-binding mutation impaired leading strand recycling. We propose that Mrc1 toggles histones between the lagging and leading strand recycling pathways, in part by intra-replisome co-chaperoning, to ensure epigenetic transmission to both daughter cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Schizosaccharomyces
/
Histonas
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Proteínas de Schizosaccharomyces pombe
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Epigênese Genética
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Replicação do DNA
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article