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The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks.


ABSTRACT: The Bloom syndrome helicase BLM interacts with topoisomerase III? (TOP3A), RMI1 and RMI2 to form the BTR complex, which dissolves double Holliday junctions to produce non-crossover homologous recombination (HR) products. BLM also promotes DNA-end resection, restart of stalled replication forks, and processing of ultra-fine DNA bridges in mitosis. How these activities of the BTR complex are regulated in cells is still unclear. Here, we identify multiple conserved motifs within the BTR complex that interact cooperatively with the single-stranded DNA (ssDNA)-binding protein RPA. Furthermore, we demonstrate that RPA-binding is required for stable BLM recruitment to sites of DNA replication stress and for fork restart, but not for its roles in HR or mitosis. Our findings suggest a model in which the BTR complex contains the intrinsic ability to sense levels of RPA-ssDNA at replication forks, which controls BLM recruitment and activation in response to replication stress.

SUBMITTER: Shorrocks AK 

PROVIDER: S-EPMC7838300 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks.

Shorrocks Ann-Marie K AK   Jones Samuel E SE   Tsukada Kaima K   Morrow Carl A CA   Belblidia Zoulikha Z   Shen Johanna J   Vendrell Iolanda I   Fischer Roman R   Kessler Benedikt M BM   Blackford Andrew N AN  

Nature communications 20210126 1


The Bloom syndrome helicase BLM interacts with topoisomerase IIIα (TOP3A), RMI1 and RMI2 to form the BTR complex, which dissolves double Holliday junctions to produce non-crossover homologous recombination (HR) products. BLM also promotes DNA-end resection, restart of stalled replication forks, and processing of ultra-fine DNA bridges in mitosis. How these activities of the BTR complex are regulated in cells is still unclear. Here, we identify multiple conserved motifs within the BTR complex tha  ...[more]

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