Homologous recombination articles from across Nature Portfolio

This study presents the crystal structure of a BRCA2-DMC1 complex revealing how BRCA2’s PhePP motifs stabilise RAD51 and DMC1 nucleoprotein filaments during DNA double-strand break repair by mitotic and meiotic recombination.

Using highly purified protein factors, we provide evidence that BRCA1–BARD1 physically interacts with EXO1, BLM and WRN and upregulates the activity of all three resection pathways.

DSS1 is crucial for BRCA2 dependent genome repair. Here, the authors reveal how DSS1 restricts the dsDNA binding ability of BRCA2 to ensure BRCA2/RAD51 loading on ssDNA. Mutations in DSS1 disrupt this regulation, leading to impaired DNA repair, replication fork protection and R-loop suppression.

Fanconi anemia proteins are required for repair of DNA interstrand crosslinks. Here, the authors show that these proteins are also recruited to DNA double-strand breaks to promote repair by homologous recombination.

Successful meiotic homologous recombination relies on the tight regulation of RAD51 and DMC1 strand exchange proteins. This study shows that the conserved FIGNL1-FIRRM complex plays a critical role for fertility by restraining uncontrolled assembly of RAD51 and DMC1 filament during meiosis.

Homologous recombination in CRISPR–Cas9 genome editing is increased by blocking an exonuclease activity.

Increasing evidence links RNA methyltransferases to DNA damage repair. METTL16 is now shown to antagonize homologous recombination by preventing DNA-end resection via MRE11. Thus, METTL16 may represent a cancer vulnerability that can be used to identify patients able to benefit from combination therapies with DNA-damaging agents.

Emerging findings provide compelling evidence that the BRCA1-binding partner BARD1 contributes yet further to BRCA1 function. BARD1 is crucial for positioning the E2 ubiquitin-conjugating enzyme that confers specificity of its ligase to residues on histone H2A, and BARD1 also promotes DNA damage–induced chromatin recruitment through an interaction with ubiquitin-conjugated Lys13 or Lys15 of H2A on the nucleosome core particle.

Replication stress fuels chromosomal instability, tumor heterogeneity and therapy resistance. The Sonic hedgehog pathway is now linked to an unorthodox form of replication stress in cerebellar granular-cell progenitors through deregulated firing of DNA replication origins, with implications for the pathogenesis, genomic instability and treatment of medulloblastoma.

Cyclic GMP–AMP synthase (cGAS) inhibits DNA damage repair in the nucleus and thereby promotes tumorigenesis.