NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

Nucleic Acids Research
Ann C ParplysClaudia Wiese

Abstract

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 pathw...Continue Reading

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Citations

Aug 20, 2016·Oncotarget·Yangbo YueClaudia Wiese
Mar 9, 2019·Molecular and Clinical Oncology·Laura GiuntiIacopo Sardi
Sep 3, 2020·The Journal of Cell Biology·David G MaranonClaudia Wiese
Apr 6, 2018·BioMed Research International·Pengru HuangLili Cui
Apr 3, 2018·Genes & Genetic Systems·Wenqing ZhuHao Pang
Jun 3, 2021·International Journal of Molecular Sciences·Mayes Alswady-HoffShanbeh Zienolddiny

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Methods Mentioned

BETA
transfection
transfections
flow cytometry
chromosomal aberrations
PCR
gel filtration
electrophoresis
pull-down
PCA
immunoprecipitation

Software Mentioned

Image J
BioSig Imaging Bioinformatics Platform
Quantity One
ImageJ
ClustalW
Prism
FlowJo
GraphPad
BLAST

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