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The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress.

Yw, Zhang J, Brognard C, Coughlin Z, You M, Dolled-Filhart A, Aslanian G, Manning Rt, Abraham T, Hunter

Published in Molecular Cell

ATR and Chk1 are two key protein kinases in the replication checkpoint. Activation of ATR-Chk1 has been extensively investigated, but checkpoint termination and replication fork restart are less well understood. Here, we report that DNA damage not only activates Chk1, but also exposes a degron-like region at the carboxyl terminus of Chk1 to an Fbx6...

CtIP links DNA double-strand break sensing to resection.

You, Zhongsheng Shi, Linda Z Zhu, Quan Wu, Peng Zhang, You-Wei Basilio, Andrew Tonnu, Nina Verma, Inder M Berns, Michael W Hunter, Tony ...

Published in Molecular cell

In response to DNA double-strand breaks (DSBs), cells sense the DNA lesions and then activate the protein kinase ATM. Subsequent DSB resection produces RPA-coated ssDNA that is essential for activation of the DNA damage checkpoint and DNA repair by homologous recombination (HR). However, the biochemical mechanism underlying the transition from DSB ...

Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy.

Wilkinson, Deepti S Jariwala, Jinel S Anderson, Ericka Mitra, Koyel Meisenhelder, Jill Chang, Jessica T Ideker, Trey Hunter, Tony Nizet, Victor Dillin, Andrew ...

Published in Molecular cell

The protein LC3 is indispensible for the cellular recycling process of autophagy and plays critical roles during cargo recruitment, autophagosome biogenesis, and completion. Here, we report that LC3 is phosphorylated at threonine 50 (Thr(50)) by the mammalian Sterile-20 kinases STK3 and STK4. Loss of phosphorylation at this site blocks autophagy by...

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