A High Resolution Snapshot Of DNA Repair

Scientists in China have visualized the structure of a key DNA repair component at near-atomic resolution.

AsianScientist (Dec. 7, 2017) – In a study published in Science, a team of researchers at the University of Science and Technology China (USTC) have visualized the structure of a key DNA repair enzyme at near-atomic resolution.

Cells continuously replicate to repair and replace damaged tissue, and each division requires a reprinting of the cells’ genetic blueprints. As the DNA duplicates errors inevitably occur, resulting in damage that, if left unrepaired, can lead to cellular death.

The ATR kinase is one of six proteins responsible for maintaining the health of the cell. When this family of proteins identify a problem, such as DNA damage, they instigate the downstream signals needed to repair the damage.

In this study, researchers led by professor Cai Gang of USTC have imaged the ATR kinase protein at unprecedented resolution, and are beginning to understand its response to DNA damage. They used electron microscopy to image the Mec1-Ddc2 complex at 3.9 ångströms, which is about eight times the size of a single atom of helium. The complex is found in yeast and is the equivalent of the human ATR protein and its cell-signaling protein partner, ATRIP.

“Cryo-electron microscopy of the Mec1-Ddc2 with state-of-the-art instrumentation has resulted in an electron density map at near-atomic resolution,” said Cai, noting that the improved map has confirmed and expanded upon previous findings.

The high-resolution structural information revealed regulatory sites of the ATR kinase, which are poised to activate at the first hint of DNA damage. Elucidating this mechanism could aid in the development of new therapeutics.

“The structure of the Mec1-Ddc2 complex in yeast closely resembles that of the human counterpart,” said Cai. “We believe the information acquired from our study sheds light on the architecture and mechanism of the human ATR-ATRIP complex.”

Cai and his team are now imaging the yeast Mec1-Ddc2 and its human counterpart at different points of activation. They plan to develop more specific and efficient ATR inhibitors to explore the possibility of improving cancer treatments.

The article can be found at: Wang et al. (2017) 3.9 Å Structure of the Yeast Mec1-Ddc2 Complex, a Homolog of Human ATR-ATRIP.


Source: University of Science and Technology of China.
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