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nature research | reporting summary

April 2018

Data

Policy information about availability of data

All manuscripts must include a data availability statement. This statement should provide the following information, where applicable:

• Accession codes, unique identifiers, or web links for publicly available datasets


• A list of figures that have associated raw data


• A description of any restrictions on data availability
  irCLIP data is available via GEO under the accession number GSE109026. All uncropped blots are provided in Supplementary Figure 1. Data underlying the graphical
  representations used in the figures, including all experiments presenting data from animal models, are provided as a Source Data File. Exact (p) values and defined
  sample size (n) are provided in Supplementary Data 1.

Field-specific reporting

Please select the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences

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Life sciences study design

All studies must disclose on these points even when the disclosure is negative.

Sample size For each experimental type, an appropriate number of data points or experiments were collected. For animal or cell line based experiments,

at least 3 independently derived samples were measured. For example, deep sequencing experiments were performed in duplicate, each

mice genotype data were collected on more than 3 individuals from more than 2 independent crosses.

Data exclusions No data were excluded from the analysis.

Replication As no data were excluded, all values from each experiment are presented and the variation can be seen in the figures. Statistical analysis as

described throughout the manuscript provided the ability to confidently assess differences between different experimental conditions. More

information and details can be found on Supplemental Data 1. All mouse phenotype analyses were done multiple times independently with

more than 3 mice from at least 2 independent crosses. Only results that can be successfully repeated were included in the manuscript.

Randomization Randomization was not performed, however biological replicate experiments were performed on different days. For the animal and mouse

cell line based experiments, the samples are allocated based on on genotypes (confirmed and validated via PCR).

Blinding No blinding was used during the experimentation. The mutant mice were visibly smaller, genotypes have to be determined ahead of the

experiments to plan complicated analyses.

Reporting for specific materials, systems and methods

Materials & experimental systems

n/a Involved in the study

Unique biological materials

Antibodies

Eukaryotic cell lines

Palaeontology

Animals and other organisms

Human research participants

Methods

n/a Involved in the study

ChIP-seq

Flow cytometry

MRI-based neuroimaging

Antibodies

Antibodies used [Human Antibodies for Westerns (dilution 1:2000): pDNA-PKcs S2056 (Abcam, ab18192, lot. GR296008-1) and T2609 clone 10B1

(ab18356, lot. GR309667-22), DNA-PKcs (Novus Biologicals, NBP2-33995, lot. R32563), DNA-PKcs (Bethyl, A303-967A), Ku80

(Bethyl, A302-627A and Novus, NBP2-373583, lot. 140928) and p53 clone 1C12 (Cell Signaling, 2524S, lot. 13)]. Rabbit IgG

(ThermoFisher Scientific, 02-6102, lot. Dilution 1:10,000 ). Secondary antibodies include Alexa-Fluor 488, 568, and 647 (Life

Technologies). Antibodies for FACS analysis: biotin anti-mouse CD4 (cat. 100404, clone GK1.5, lot. B245033), biotin anti-mouse