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Recruitment but no repair

A repair protein (green) that lacks its kinase activity (left) or phosphorylation sites (right) still turns up at the repair site (blue).

ADNA repair protein turns up at the job site even without its tool kit, according to Uematsu et al. (page 219). Its visit is then prolonged by its inefficiency.

Fixing double strand breaks in DNA by nonhomologous end joining (NHEJ) requires a DNA-dependent protein kinase (DNA-PK) to bind to the loose ends of broken DNA and a ligase to do the gluing. This protein machinery must turn up and fix the ends rapidly to minimize the chance that DNA diffusion causes the wrong partners to be glued back together.

Very little is known, however, about the in vivo dynamics of NHEJ. Here, Uematsu et al. describe the dynamics of DNA–PK recruitment in vivo. DNA-PK is composed of two subunits: Ku70/80 and DNA-PK_CS. They found that both subunits accumulated at damaged sites within two seconds after targeted DNA breakage. This repair site recruitment was dependent on the Ku70/80 subunit.

DNA-PK_CS has a kinase domain and a cluster of phosphorylation sites, both of which are needed for mending DNA. Mutation of either, however, did not impair the enzyme's recruitment speed.

Despite turning up for work as usual, the mutant repair proteins didn't leave as quickly as the wild type. DNA-PK_CS is well-known for performing autophosphorylation, and this ability is necessary for DNA repair. Since recruitment of the mutant proteins was normal but repair was deficient, the authors suggest that the main target of DNA-PK_CS kinase activity is itself. Autophosphorylation might be the signal that the two loose DNA ends have come together. It most likely triggers the release of DNA-PK and allows access for the ligase to do its gluing.

Ruth Williams

ruth.williams{at}rockefeller.edu

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Related Article

Autophosphorylation of DNA-PK_CS regulates its dynamics at DNA double-strand breaks

Naoya Uematsu, Eric Weterings, Ken-ichi Yano, Keiko Morotomi-Yano, Burkhard Jakob, Gisela Taucher-Scholz, Pierre-Olivier Mari, Dik C. van Gent, Benjamin P.C. Chen, and David J. Chen
J. Cell Biol. 2007 177: 219-229. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 943K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Related Collections Related Article Social Bookmarking                            What's this?