We demonstrate that the MCM8-9 complex forms hexamers, and that hexamers are necessary for DNA unwinding (3/n)

Productive hexameric complexes assemble from dimeric MCM8-9 on DNA in the presence of ATP, forming rings that encircle DNA, while complexes formed in solution without DNA are non-productive (4/n)

The hexamer of MCM8-9 involves two distinct interfaces; viewing from the C-terminal side, the interface between MCM8 and MCM9 is stable, forming an obligate heterodimer, while the interface between MCM9 and MCM8 is dynamic, forming the hexamer (5/n)

HROB binding across the stable interface causes a conformational change of the MCM8-9 complex, which stimulates DNA unwinding (maybe similarly to GINS-Cdc45 or MCM10 with respect to MCM2-7) - an interesting nut to crack for structural biologists (7/n)

So, somewhat surprisingly, HROB does not promote DNA binding or hexameric ring formation of MCM8-9 on DNA, but it rather stimulates MCM8-9 downstream of loading (8/n)

As light illuminates your scientific discoveries with mass photometry, may it also illuminate your festive celebrations. Happy Diwali from Team Refeyn! 🎉🎉🎉

Check out our pre-print showing a direct function of the BRCA1-BARD1 tumor suppressor in the initial steps of DNA break repair (resection). Very similar data will be coming also from the The Sung Lab at UTHSCSA laboratory. researchsquare.com/article/rs-363…

This Methods paper is now available for those who want to try out our site-specific labeling strategies for human RPA. sciencedirect.com/science/articl… Congrats Vikas Kaushik for tackling this challenge.

Important development!! Very glad to share that Anand lab is open for business IMB Mainz . We will be investigating (mostly) HDR repair pathways using biochemistry and single-molecule imaging methods. Looking for motivated PhD students and a technician.

If you are interested in pursuing PhD in Genome stability and related research area, apply to IPP program. PhD position available in my lab as well. Check out the given below link to find out more. Spread the word. ...

Wrapping of single-stranded DNA by Replication Protein A and modulation through phosphorylation biorxiv.org/content/10.110…

As a former IISERite, strongly recommended!

Here is our latest paper together with Raphael Guerois on the MCM8-9 helicase complex and its activation by HROB. Congratulations to Ananya Acharya and many thanks to Alberto Ciccia and Ralf Seidel labs nature.com/articles/s4146…

A new study from the Cejka Lab identified how HROB promotes #dna unwinding by the MCM8-9 helicase in DNA repair. Congratulations to 👏Ananya Acharya! USI University Nature Communications tinyurl.com/5n7sc7ze

Molecular insights into the activation of Mre11-Rad50 endonuclease activity by Sae2/CtIP: cell.com/molecular-cell… Check this new paper by our lab, Raphaël Guérois' and Cejka Lab where Alphafold, biochemistry and yeast genetics uncover how pSae2/pCtIP activates Mre11 nuclease!

Check out our latest paper showing that HLTF removes Cas9 from DNA, explaining phenotypic differences when using the two Cas9 nickase variants. Important for gene editing! Thanks to Giordano Reginato & Rosaria and Martin Jinek Taekjip Ha andre nussenzweig lab nature.com/articles/s4146…

1/7 Our latest preprint is out! 🚨 Sourav Agrawal | ସୌରଭ , Xiuhua Lin , Vivek Susvirkar et al. discover human RPA is a critical telomerase processivity factor essential for telomere maintenance. This reshapes our understanding of human telomerase regulation. biorxiv.org/content/10.110…

Happy to announce our new publication in Nature Communications, spearheaded by super-talented project leader M@x R. . We identified that helicase loading is a self-limiting reaction supporting equal distribution of the replicative helicase across the genome. rdcu.be/dRTAZ

We are thrilled to present you our work on BRCA1-BARD1 nature showing that the complex has a direct role in long-range DNA end resection. With Ilaria_Ceppi Maria Rosaria Dello Stritto and our collaborators Pablo Huertas' Lab Sylvie Noordermeer and Seidel labs. nature.com/articles/s4158…