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19.09.16 Fine details teased out in pathway of DNA repair by homologous recombination

last modified Oct 25, 2016 10:32 AM
Steve Jackson's lab pin down further events in the DNA repair pathway in this Nature Communications paper
19.09.16 Fine details teased out in pathway of DNA repair by homologous recombination

Excerpt from Fig. 5e in the paper: proposed model for repair of single-ended DNA double-strand breaks

Coordinated nuclease activities counteract Ku at single-ended DNA double-strand breaks

Chanut P, Britton S, Coates J, Jackson SP, Calsou P. Nat Commun. (2016) 7:12889 DOI 10.1038/ncomms12889    [PMID: 27641979]

 

Abstract from the paper:

Repair of single-ended DNA double-strand breaks (seDSBs) by homologous recombination (HR) requires the generation of a 3' single-strand DNA overhang by exonuclease activities in a process called DNA resection. However, it is anticipated that the highly abundant DNA end-binding protein Ku sequesters seDSBs and shields them from exonuclease activities. Despite pioneering works in yeast, it is unclear how mammalian cells counteract Ku at seDSBs to allow HR to proceed. Here we show that in human cells, ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on seDSBs. We also provide evidence for a hitherto unsuspected additional mechanism that contributes to prevent Ku accumulation at seDSBs, acting downstream of MRE11 endonuclease activity and in parallel with MRE11 exonuclease activity. Finally, we show that Ku persistence at seDSBs compromises Rad51 focus assembly but not DNA resection.

 

Abstract and figure reproduced under Creative Commons CC BY 4.0.

 

Read more about research in the Jackson lab.

Watch Steve Jackson describe his research on video.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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