Rtt105 functions as a chaperone for replication protein A to preserve genome stability.
EMBO J
; 37(17)2018 09 03.
Article
em En
| MEDLINE
| ID: mdl-30065069
ABSTRACT
Generation of single-stranded DNA (ssDNA) is required for the template strand formation during DNA replication. Replication Protein A (RPA) is an ssDNA-binding protein essential for protecting ssDNA at replication forks in eukaryotic cells. While significant progress has been made in characterizing the role of the RPA-ssDNA complex, how RPA is loaded at replication forks remains poorly explored. Here, we show that the Saccharomyces cerevisiae protein regulator of Ty1 transposition 105 (Rtt105) binds RPA and helps load it at replication forks. Cells lacking Rtt105 exhibit a dramatic reduction in RPA loading at replication forks, compromised DNA synthesis under replication stress, and increased genome instability. Mechanistically, we show that Rtt105 mediates the RPA-importin interaction and also promotes RPA binding to ssDNA directly in vitro, but is not present in the final RPA-ssDNA complex. Single-molecule studies reveal that Rtt105 affects the binding mode of RPA to ssDNA These results support a model in which Rtt105 functions as an RPA chaperone that escorts RPA to the nucleus and facilitates its loading onto ssDNA at replication forks.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Genoma Fúngico
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Chaperonas Moleculares
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Proteínas de Saccharomyces cerevisiae
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Instabilidade Genômica
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Proteína de Replicação A
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Modelos Biológicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China