🐭 In vivo veritas 🐭 Now out in Nature Genetics: @josjonkers.bsky.social and I describe currently available mouse models of BRCA1/2 and their roles in understanding BRCA1/2 biology, particularly in normal development, tumor suppression and therapy response. www.nature.com/articles/s41...

Honoured (and excited!) I was named among this year's Birnstiel awardees for my PhD work! 🎉

Nature research paper: NASP modulates histone turnover to drive PARP inhibitor resistance go.nature.com/45vRWhd

💡 Take-home: Histone eviction is an immediate response to PARPi treatment and cancer cells are require an INO80–NASP–PARP1 axis for survival. Targeting histone turnover could therefore overcome drug resistance. (7/8)

However, NASP cannot do it all. It is supported by (1) the INO80 complex which remodels chromatin to evict histones, (2) which NASP then stabilises and stores and (3) PARP1 and other factors help reincorporate them. (6/8)

Lose NASP and even resistant tumor cells become resistant to PARPi. (5/8)

What are the factors mediating this histone release? To answer this we performed genome-wide genetic screens and identified NASP, a histone chaperone, as essential for handling these evicted histones. (4/8)

The answer was puzzling: Histones got kicked off the chromatin upon PARPi exposure. These free histones must be stored & recycled, otherwise cancer cells struggle to survive. (3/8)

PARP inhibitors (PARPi) have clearly been a game changer for homologous recombination-deficient tumours, but therapy resistance remains a challenge. The impact of PARPi on DNA integrity has been very well described, but we wondered what happens to the chromatin environment? 🧬 (2/8)

Thrilled to share our latest work, just published in @nature.com ⬇ www.nature.com/articles/s41... We discovered that PARP inhibitors 💊 trigger histone eviction from the chromatin and this creates a hidden vulnerability in PARPi resistant tumors. 🧵 (1/8)

Today, these amazing NKI researchers are pushing their limits by climbing the Alpe d’Huez. Go for it lovely people! We are proud to see so many of you dedicate your time and effort to supporting cancer research. With @oncodeinstitute.bsky.social #AlpedHuZes #cancerresearch #ad6 #NKI

A great read for your Monday morning! 🧬

30 years after the discovery of the BRCA1/2 genes, Khalizieva et al. provide a historical account of the key discoveries in BRCA1/2 genetics that contributed to our understanding of their function in DNA repair and cancer. Learn more here: ➡️ tinyurl.com/gd352083

Happy to have contributed to this issue 🎉 @akhalizieva.bsky.social did an amazing job exploring our current knowledge on our two favourite genes, BRCA1 and BRCA2, and how this is being used to target BRCA1/2-mutated tumors. Check it out ⬇️ genesdev.cshlp.org/content/39/1...

NEW ISSUE !!! Leading scientists come together to discuss recent advances in cancer biology in this collection of comprehensive Reviews spanning different cancer types and various aspects of cancer biology. Learn more here: ➡️ genesdev.cshlp.org/content/curr...