17. Dual inhibition of DNA-PK and DNA polymerase theta overcomes radiation resistance induced by p53 deficiency - Kumar et al. doi.org/10.1093/narc.... Dual DNA-PK/POLθ inhibition restores radiation sensitivity in p53-deficient models. 18/18

16. #CDK2 regulates collapsed replication fork repair in CCNE1-amplified ovarian cancer cells via homologous recombination - Brown et al. doi.org/10.1093/narc.... Addresses the session's cell-cycle/replication repair interface by connecting cyclin-CDK2 activity to HR repair of collapsed forks. 17/18

15. Harnessing transcriptional regulation of alternative end-joining to predict cancer treatment - Espín et al. doi.org/10.1093/narc... Links #hypoxia/HIF1α and #MYC to #PARP1/POLQ expression and alternative end joining, with combination-treatment effects in cancer cells. 16/18

14. Targeting DNA repair mechanisms in cancer therapy: the role of #smallmolecule #DNArepair inhibitors - Jeong et al. doi.org/10.1093/narc... “Editor’s Choice” review article detailing the current pipeline of repair inhibitors, synthetic lethality, biomarkers, and their combinations. 15/18

13. Regulation and #pharmacological targeting of #RAD51 in cancer - Grundy et al. doi.org/10.1093/narc.... Review article on RAD51, the central recombinase regulated by BRCA2, PALB2 and RAD51 paralogs, linking HR control to #cancerprevention and #therapeuticresistance. 14/18

12. Defining the mutation signatures of #DNApolymeraseθ in cancer genomes - Hwang et al. doi.org/10.1093/narc.... Links BRCA loss to dependence on polymerase theta–mediated end joining and the resulting mutational landscape. 13/18

11. Characterization of a RAD51C-silenced high-grade serous #ovarian cancer model during development of PARP inhibitor resistance - Hurley et al. doi.org/10.1093/narc.... A non-mutational route to PARP inhibitor resistance through loss of RAD51C #promotermethylation and restored expression. 12/18

10. #Homologous recombination, cancer and the ‘RAD51 paradox’ - Matos-Rodrigues et al.
doi.org/10.1093/narc.... BRCA1, BRCA2, PALB2 and RAD51-associated factors placed within HR, replication-fork maintenance, cancer susceptibility, and the consequences of dysregulated recombination. 11/18

9. High-level tumour #methylation of #BRCA1 and #RAD51C is required for #homologousrecombination deficiency in solid cancers - Xu et al doi.org/10.1093/narc.... Extends BRCA-network deficiency beyond sequence mutations to #epigeneticsilencing. 10/18

8. #RAD51 recruitment but not replication fork stability associates with PARP inhibitor response... - Talens et al. doi.org/10.1093/narc.... Irradiation-induced RAD51 foci predict #olaparibresponse in the #ovarianPDX cohort, whereas fork protection does not. 9/18

7. Therapeutic disruption of RAD52–ssDNA complexation via novel drug-like inhibitors - Bhat et al. doi.org/10.1093/narc.... A concrete example of emerging therapeutics: identifies and optimizes RAD52 inhibitors with selective toxicity in BRCA-mutant cells. 8/18

6. #XRCC1 promotes replication restart, nascent fork degradation, and mutagenic DNA repair... Eckelmann et al. doi.org/10.1093/narc.... How does an alternative repair scaffold support BRCA2-deficient cells through altered fork processing and mutagenic repair? 7/18

5. Advancing inducible gene-inactivation systems to explore synthetic lethality - Sánta et al. doi.org/10.1093/narc.... Combined BRCA1 and RAD18 loss compromises fork restart and post-replicative gap filling, producing ssDNA gaps and replication catastrophe. 6/18

4. The RRM domains of PARP14 mediate replication fork degradation in BRCA2-deficient cells - Hale et al. doi.org/10.1093/narc.... How #PARP14 engages nascent DNA and recruits MRE11 to degrade reversed forks in BRCA2-deficient cells. 5/18

3. Mechanisms of PARP1 inhibitor resistance and their implications for cancer treatment - Jackson & Moldovan. doi.org/10.1093/narc... #HRrestoration, #replication-fork stabilization, #ssDNA-gap suppression, and strategies to overcome PARP inhibitor resistance. 4/18

2. RAD51C breast cancer-identified variants with attenuated homologous recombination function... Ganesan et al.
doi.org/10.1093/narc... #RAD51C variants retain partial #HR yet disrupt replication and accumulate gaps; a subset sensitizes cells to combined #PARP1 and #ATR inhibition. 3/18

1.STN1 upregulation promotes #PARPiresistance in BRCA2-deficient cancer cells via replication fork protection... Laghari et al. #BRCA2 loss, #RAD51 loading, #MRE11 exclusion, #forkprotection, and suppression of ssDNA gaps linked to #PARPi resistance doi.org/10.1093/narc... 2/18

⭐ How does the #BRCA network protect genome stability, and how can its vulnerabilities guide #cancertreatment? Explore 17 #NARCancer articles curated for the NAR Journals’ RRS session. #RadiationResearchSocietyMeeting #DNARepair @aibsbiology.bsky.social @nar-cancer-editor.bsky.social 1/18

The Human Genome Project didn’t end genomics—it opened the door.
Its sequence helped fuel #precisionmedicine, #cancergenomics, #genetherapy and #genomeediting.
And it revealed a deeper question:
🧬 How is the genome regulated? Enter the world of #Epigenetics.
#HumanGenomeProject #HGP #Genomics