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The Ku complex: recent advances and emerging roles outside of non-homologous end-joining

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Abstract

Since its discovery in 1981, the Ku complex has been extensively studied under multiple cellular contexts, with most work focusing on Ku in terms of its essential role in non-homologous end-joining (NHEJ). In this process, Ku is well-known as the DNA-binding subunit for DNA-PK, which is central to the NHEJ repair process. However, in addition to the extensive study of Ku’s role in DNA repair, Ku has also been implicated in various other cellular processes including transcription, the DNA damage response, DNA replication, telomere maintenance, and has since been studied in multiple contexts, growing into a multidisciplinary point of research across various fields. Some advances have been driven by clarification of Ku’s structure, including the original Ku crystal structure and the more recent Ku–DNA-PKcs crystallography, cryogenic electron microscopy (cryoEM) studies, and the identification of various post-translational modifications. Here, we focus on the advances made in understanding the Ku heterodimer outside of non-homologous end-joining, and across a variety of model organisms. We explore unique structural and functional aspects, detail Ku expression, conservation, and essentiality in different species, discuss the evidence for its involvement in a diverse range of cellular functions, highlight Ku protein interactions and recent work concerning Ku-binding motifs, and finally, we summarize the clinical Ku-related research to date.

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Acknowledgements

We are grateful to Mohamed Aly for reading and providing feedback on the review.

Funding

This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant and a NSERC Discovery Accelerator Supplement to C.S.P.. S.A. and G.P. were supported by Ontario Graduate Scholarships.

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  1. Robarts Research Institute and Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5B7, Canada

    Sanna Abbasi, Gursimran Parmar, Rachel D. Kelly, Nileeka Balasuriya & Caroline Schild-Poulter

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  1. Sanna Abbasi
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  2. Gursimran Parmar
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  3. Rachel D. Kelly
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Contributions

S.A. and G.P. conceptualized the idea of the review. S.A., G.P., R.D.K., and N.B. wrote the original draft and S.A., G.P, and R.D.K. prepared the figures and tables. C.S.P. provided edits, suggestions, and critical feedback. The final version of the review was edited by all authors.

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Correspondence to Caroline Schild-Poulter.

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Abbasi, S., Parmar, G., Kelly, R.D. et al. The Ku complex: recent advances and emerging roles outside of non-homologous end-joining. Cell. Mol. Life Sci. 78, 4589–4613 (2021). https://doi.org/10.1007/s00018-021-03801-1

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