Sahil Batra

Cryo-Electron Microscopy Reveals Hidden Mechanics of DNA Replication, Sheds New Light on Cancer Target MSK researchers shed new light on G-quadruplexes, a type of secondary DNA structure that has attracted attention as a potential therapeutic target in cancer.

Shout out to Sloan Kettering @mskcancercenter.bsky.social for supporting basic science / foundational biology...

www.mskcc.org/news/cryo-el...

Thanks to @dirkremus.bsky.social, Richard Hite, @benallwein.bsky.social and all the co-authors.
Thanks to @mskeducation.bsky.social, NIH, National Cancer Institute, BRIA Award @mskcancercenter.bsky.social for funding.

Unlike the bacterial hexameric ring helicases that translocate in a sequential rotary hand-over-hand mechanism, we propose CMG translocates like a 'helical inchworm', oscillating between planar and spiral states.

Importantly, the G4 traps CMG in translocation intermediate states, suggesting that CMG uses a DNA translocation mechanism that is distinct from bacterial hexameric ring helicases.

Exonuclease protection data and cryo-EM structures of the stalled CMG complexes demonstrate that the G4 is locked inside the CMG channel at the interface of the N- and C-tiers, fully folded and sequestered from G4 helicases.

We previously showed that R-loop-associated G-quadruplexes (G4s) impede replisome progression. Here, we demonstrate that a single G4 specifically in the leading strand template effectively blocks reconstituted yeast and human replisomes even in the absence of G4 stabilizers.

G-quadruplex–stalled eukaryotic replisome structure reveals helical inchworm DNA translocation DNA G-quadruplexes (G4s) are non–B-form DNA secondary structures that threaten genome stability by impeding DNA replication. To elucidate how G4s induce replication fork arrest, we characterized fork ...

Thrilled to share first part of my post-doc work, published today in @science.org www.science.org/doi/10.1126/...
We use reconstituted replication system and cryo-EM to unravel an unexpected mechanism of DNA translocation employed by eukaryotic replicative helicase.