NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability
Parplys, Ann C., Zhao, Weixing, Sharma, Neelam, Groesser, Torsten, Liang, Fengshan, Maranon, David G., Leung, Stanley G., Grundt, Kirsten, Dray, Eloise, Idate, Rupa, Ostvold, Anne Carine, Schild, David, Sung, Patrick, & Wiese, Claudia (2015) NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability. Nucleic Acids Research, 43(20), pp. 9817-9834.
NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression.
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|Item Type:||Journal Article|
|Keywords:||genome stability, homologous recombination, DNA repair, tumor suppression|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2015 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.|
|Copyright Statement:||This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http: // creativecommons.org / licenses / by-nc / 4.0 / ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact email@example.com|
|Deposited On:||12 Sep 2016 23:00|
|Last Modified:||14 Sep 2016 00:58|
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