The DNA damage response at dysfunctional telomeres, and at interstitial and subtelomeric DNA double-strand breaks
| Autor: | Keiko Muraki, John P. Murnane |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
DNA End-Joining Repair DNA damage Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics Animals Humans DNA Breaks Double-Stranded Molecular Biology fungi DNA replication Chromosome General Medicine Telomere Subtelomere Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology chemistry biological phenomena cell phenomena and immunity Chromosome breakage Homologous recombination 030217 neurology & neurosurgery DNA |
| Zdroj: | Genes & Genetic Systems. 92:135-152 |
| ISSN: | 1880-5779 1341-7568 |
| Popis: | In mammals, DNA double-strand breaks (DSBs) are primarily repaired by classical non-homologous end joining (C-NHEJ), although homologous recombination repair and alternative NHEJ (A-NHEJ), which involve DSB processing, can also occur. These pathways are tightly regulated to maintain chromosome integrity. The ends of chromosomes, called telomeres, contain telomeric DNA that forms a cap structure in cooperation with telomeric proteins to prevent the activation of the DNA damage response and chromosome fusion at chromosome termini. Telomeres and subtelomeric regions are poor substrates for DNA replication; therefore, regions near telomeres are prone to replication fork stalling and chromosome breakage. Moreover, DSBs near telomeres are poorly repaired. As a result, when DSBs occur near telomeres in normal cells, the cells stop proliferating, while in cancer cells, subtelomeric DSBs induce rearrangements due to the absence of cell cycle checkpoints. The sensitivity of subtelomeric regions to DSBs is due to the improper regulation of processing, because although C-NHEJ is functional at subtelomeric DSBs, excessive processing results in an increased frequency of large deletions and chromosome rearrangements involving A-NHEJ. |
| Databáze: | OpenAIRE |
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