DNA-PKcs suppress chromosome translocation in human cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA974458 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24661200_1.fastq.gz | Fastqsanger.gz | |||
| SRR24661200_2.fastq.gz | Fastqsanger.gz | |||
| SRR24661201_1.fastq.gz | Fastqsanger.gz | |||
| SRR24661201_2.fastq.gz | Fastqsanger.gz | |||
| SRR24661202_1.fastq.gz | Fastqsanger.gz |
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Project description:Two DNA repair pathways, non-homologous end joining (NHEJ) and alternative end joining (A-EJ), are involved in V(D)J recombination and chromosome translocation. Previous studies reported distinct repair mechanisms for chromosome translocation, with NHEJ predominantly involved in human and A-EJ in mice. NHEJ depends on DNA-PKcs, a critical partner in synapsis formation and downstream component activation. While DNA-PKcs inhibition promotes chromosome translocations harboring microhomologies in mice, its synonymous effect in human is not known. We find partial DNA-PKcs inhibition in human cell lines leads to increased genome-wide translocations composed mostly of direct joints, indicating the continued involvement of dampened NHEJ in these processes. In contrast, complete DNA-PKcs inhibition and genetic inhibition DNA-PKcs kinase domain substantially increased microhomology-mediated end joining (MMEJ), thus bridging the two different translocation mechanisms between human and mice. Similar to a previous study on Ku70 deletion, DNA-PKcs deletion in G1/G0-phase mouse pro-B cell lines, impair the recombination of RAG1/2-mediated DNA double-strand breaks (DSBs). This DNA-PKcs-deficient repair mechanism exhibited reduced V(D)J recombination efficiency, increased end resection, decreased polymerase-mediated insertions, loss of recombination fidelity and generated relatively higher rates of chromosome translocation as a consequence of dysregulated coding and signal end joining. Our study underscores DNA-PKcs in suppressing illegitimate chromosome rearrangement in both species.
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