CRISPR mechanism of action and potentials target genes (IMAGE)
Caption
CRISPR “spacer” sequences are transcribed into short RNA sequences (single guide RNA-sgRNA) capable of guiding the system toward matching or complementary DNA sequences. When the target DNA is found, Cas9 binds to the DNA and cuts it, generating DNA double-strand breaks (DSBs). Then, the DSB repair pathway, including homologous recombination (HR) and non-homologous DNA end joining (NHEJ), is activated to repair DSBs. The error-prone NHEJ pathway can lead to random indel mutations in the binding site. Indel mutations that occur within the coding region of a gene, can lead to gene knockout. CRISPR-Cas9 has been used in breast cancer research to edit oncogenes and tumor suppressors genes, leading to their inactivation or activation, respectively. ACKR3, Atypical Chemokine Receptor 3; BRCA1, Breast cancer type 1; Cas9, CRISPR associated protein 9; CRISPR, clustered regularly interspaced short palindromic repeat; CXCR4, C-X-C Motif Chemokine Receptor 4; DSBs, DNA double-strand breaks; HR, homologous recombination; HER2, human epidermal growth factor receptor 2; MYC, MYC Proto-Oncogene; NHEJ, non-homologous DNA end joining; OPN, osteopontin gene; PAM, Protospacer Adjacent Motif; PTEN, Phosphatase and Tensin homolog; sgRNA, single guide RNA; TP53, Tumor Protein P53.
Credit
Milena Rondón-Lagos, Nelson Rangel
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CC BY-NC