Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing
He, Liu; Lever, Rebecca; Cubbon, Andrew; Tehseen, Muhammad; Jenkins, Tabitha; Nottingham, Alice O.; Horton, Anya; Betts, Hannah; Fisher, Martin; Hamdan, Samir M.; Soultanas, Panos; Bolt, Edward L.
Alice O. Nottingham
Samir M. Hamdan
PANOS SOULTANAS PANOS.SOULTANAS@NOTTINGHAM.AC.UK
Professor of Biological Chemistry
ED BOLT ED.BOLT@NOTTINGHAM.AC.UK
DNA strand breaks are repaired by DNA synthesis from an exposed DNA end paired with a homologous DNA template. DNA polymerase delta (Pol δ) catalyses DNA synthesis in multiple eukaryotic DNA break repair pathways but triggers genome instability unless its activity is restrained. We show that human HelQ halts DNA synthesis by isolated Pol δ and Pol δ-PCNA-RPA holoenzyme. Using novel HelQ mutant proteins we identify that inhibition of Pol δ is independent of DNA binding, and maps to a 70 amino acid intrinsically disordered region of HelQ. Pol δ and its POLD3 subunit robustly stimulated DNA single-strand annealing by HelQ, and POLD3 and HelQ interact physically via the intrinsically disordered HelQ region. This data, and inability of HelQ to inhibit DNA synthesis by the POLD1 catalytic subunit of Pol δ, reveal a mechanism for limiting DNA synthesis and promoting DNA strand annealing during human DNA break repair, which centres on POLD3.
He, L., Lever, R., Cubbon, A., Tehseen, M., Jenkins, T., Nottingham, A. O., …Bolt, E. L. (2023). Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing. Nucleic Acids Research, 51(4), 1740-1749. https://doi.org/10.1093/nar/gkad032
|Journal Article Type||Article|
|Acceptance Date||Jan 10, 2023|
|Online Publication Date||Jan 31, 2023|
|Publication Date||Feb 28, 2023|
|Deposit Date||Feb 6, 2023|
|Publicly Available Date||Feb 7, 2023|
|Journal||Nucleic acids research|
|Publisher||Oxford University Press|
|Peer Reviewed||Peer Reviewed|
Interaction of human HelQ with DNA polymerase delta
Publisher Licence URL
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.