SLX4-XPF mediates DNA damage responses to replication stress induced by DNA-protein interactions.
J Cell Biol
; 220(1)2021 01 04.
Article
em En
| MEDLINE
| ID: mdl-33347546
ABSTRACT
The DNA damage response (DDR) has a critical role in the maintenance of genomic integrity during chromosome replication. However, responses to replication stress evoked by tight DNA-protein complexes have not been fully elucidated. Here, we used bacterial LacI protein binding to lacO arrays to make site-specific replication fork barriers on the human chromosome. These barriers induced the accumulation of single-stranded DNA (ssDNA) and various DDR proteins at the lacO site. SLX4-XPF functioned as an upstream factor for the accumulation of DDR proteins, and consequently, ATR and FANCD2 were interdependently recruited. Moreover, LacI binding in S phase caused underreplication and abnormal mitotic segregation of the lacO arrays. Finally, we show that the SLX4-ATR axis represses the anaphase abnormality induced by LacI binding. Our results outline a long-term process by which human cells manage nucleoprotein obstacles ahead of the replication fork to prevent chromosomal instability.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
/
Dano ao DNA
/
DNA
/
Recombinases
/
Proteínas de Ligação a DNA
/
Replicação do DNA
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão