Structural insights into BCDX2 complex function in homologous recombination.
Nature
; 619(7970): 640-649, 2023 Jul.
Article
in En
| MEDLINE
| ID: mdl-37344589
ABSTRACT
Homologous recombination (HR) fulfils a pivotal role in the repair of DNA double-strand breaks and collapsed replication forks1. HR depends on the products of several paralogues of RAD51, including the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 (BCDX2)2. BCDX2 functions as a mediator of nucleoprotein filament assembly by RAD51 and single-stranded DNA (ssDNA) during HR, but its mechanism remains undefined. Here we report cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis yields insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Moreover, our cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer3-6 inactivate DNA binding and the HR mediator activity of BCDX2. Our findings shed light on the role of BCDX2 in HR and provide a foundation for understanding how pathogenic alterations in BCDX2 impact genome repair.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Multiprotein Complexes
/
DNA-Binding Proteins
/
Homologous Recombination
Limits:
Humans
Language:
En
Journal:
Nature
Year:
2023
Document type:
Article
Affiliation country:
United States