3.9 Å structure of the yeast Mec1-Ddc2 complex, a homolog of human ATR-ATRIP

Key DNA repair component imaged in exquisite detail

26 December 2018

A near-atomic structural map of a master repair protein that is integral to fixing DNA damage could help drug developers to create new kinds of anti-cancer treatments.

Using electron microscopy, a team led by researchers at the University of Science and Technology of China determined the high-resolution structure of the yeast equivalent of the human ATR protein in tandem with its cell-signaling partner, ATRIP. These proteins form a complex that activates the cell’s built-in repair system at the first hint of DNA damage or errors in replication.

The detailed protein architecture — imaged to a resolution of 3.9 ångströms, about eight times the size of a single helium atom — revealed critical sites of regulation and activation that could serve as targets for future drug design efforts.

By inhibiting this complex, researchers hope to make cancer cells more sensitive to DNA-damaging chemotherapy or radiation.

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References

1. Science 358, 1206–1209 (2017). doi: 10.1126/science.aan8414