Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F24%3A00081510" target="_blank" >RIV/00159816:_____/24:00081510 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/24:00137161
Result on the web
<a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11514458/" target="_blank" >https://pmc.ncbi.nlm.nih.gov/articles/PMC11514458/</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkae770" target="_blank" >10.1093/nar/gkae770</a>
Alternative languages
Result language
angličtina
Original language name
Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA
Original language description
Homologous recombination (HR) factors are crucial for DSB repair and processing stalled replication forks. RAD51 paralogs, including RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3, have emerged as essential tumour suppressors, forming two subcomplexes, BCDX2 and CX3. Mutations in these genes are associated with cancer susceptibility and Fanconi anaemia, yet their biochemical activities remain unclear. This study reveals a linear arrangement of BCDX2 subunits compared to the RAD51 ring. BCDX2 shows a strong affinity towards single-stranded DNA (ssDNA) via unique binding mechanism compared to RAD51, and a contribution of DX2 subunits in binding branched DNA substrates. We demonstrate that BCDX2 facilitates RAD51 loading on ssDNA by suppressing the cooperative requirement of RAD51 binding to DNA and stabilizing the filament. Notably, BCDX2 also promotes RAD51 loading on short ssDNA and reversed replication fork substrates. Moreover, while mutants defective in ssDNA binding retain the ability to bind branched DNA substrates, they still facilitate RAD51 loading onto reversed replication forks. Our study provides mechanistic insights into how the BCDX2 complex stimulates the formation of BRCA2-independent RAD51 filaments on short stretches of ssDNA present at ssDNA gaps or stalled replication forks, highlighting its role in genome maintenance and DNA repair. Graphical Abstract
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
R - Projekt Ramcoveho programu EK
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
1362-4962
Volume of the periodical
52
Issue of the periodical within the volume
19
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
11738-11752
UT code for WoS article
001310711000001
EID of the result in the Scopus database
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