DNA double-strand breaks: signaling, repair and the cancer connection
- PMID: 11242102
- DOI: 10.1038/85798
DNA double-strand breaks: signaling, repair and the cancer connection
Abstract
To ensure the high-fidelity transmission of genetic information, cells have evolved mechanisms to monitor genome integrity. Cells respond to DNA damage by activating a complex DNA-damage-response pathway that includes cell-cycle arrest, the transcriptional and post-transcriptional activation of a subset of genes including those associated with DNA repair, and, under some circumstances, the triggering of programmed cell death. An inability to respond properly to, or to repair, DNA damage leads to genetic instability, which in turn may enhance the rate of cancer development. Indeed, it is becoming increasingly clear that deficiencies in DNA-damage signaling and repair pathways are fundamental to the etiology of most, if not all, human cancers. Here we describe recent progress in our understanding of how cells detect and signal the presence and repair of one particularly important form of DNA damage induced by ionizing radiation-the DNA double-strand break (DSB). Moreover, we discuss how tumor suppressor proteins such as p53, ATM, Brca1 and Brca2 have been linked to such pathways, and how accumulating evidence is connecting deficiencies in cellular responses to DNA DSBs with tumorigenesis.
Similar articles
-
Nonhomologous end-joining of ionizing radiation-induced DNA double-stranded breaks in human tumor cells deficient in BRCA1 or BRCA2.Cancer Res. 2001 Jan 1;61(1):270-7. Cancer Res. 2001. PMID: 11196174
-
Regulation of ATM in DNA double strand break repair accounts for the radiosensitivity in human cells exposed to high linear energy transfer ionizing radiation.Mutat Res. 2009 Nov 2;670(1-2):15-23. doi: 10.1016/j.mrfmmm.2009.06.016. Epub 2009 Jul 5. Mutat Res. 2009. PMID: 19583974
-
E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and apoptosis.Mol Cancer Res. 2004 Apr;2(4):203-14. Mol Cancer Res. 2004. PMID: 15140942
-
The molecular and cellular basis of radiosensitivity: implications for understanding how normal tissues and tumors respond to therapeutic radiation.Cancer Invest. 1999;17(1):56-72. Cancer Invest. 1999. PMID: 10999050 Review.
-
A concise review of DNA damage checkpoints and repair in mammalian cells.Cardiovasc Revasc Med. 2006 Jul-Sep;7(3):165-72. doi: 10.1016/j.carrev.2006.02.002. Cardiovasc Revasc Med. 2006. PMID: 16945824 Review.
Cited by
-
Elucidating the genotoxicity of Fusobacterium nucleatum-secreted mutagens in colorectal cancer carcinogenesis.Gut Pathog. 2024 Sep 27;16(1):50. doi: 10.1186/s13099-024-00640-w. Gut Pathog. 2024. PMID: 39334474 Free PMC article.
-
Genetic and Epigenetic Biomarkers Associated with Early Relapse in Pediatric Acute Lymphoblastic Leukemia: A Focused Bioinformatics Study on DNA-Repair Genes.Biomedicines. 2024 Aug 5;12(8):1766. doi: 10.3390/biomedicines12081766. Biomedicines. 2024. PMID: 39200230 Free PMC article.
-
siqRNA-seq is a spike-in-independent technique for quantitative mapping of mRNA landscape.BMC Genomics. 2024 Jul 30;25(1):743. doi: 10.1186/s12864-024-10650-2. BMC Genomics. 2024. PMID: 39080556 Free PMC article.
-
Prognostic and Potential Therapeutic Roles of PRKDC Expression in Lung Cancer.Mol Biotechnol. 2024 Jul 24. doi: 10.1007/s12033-024-01209-3. Online ahead of print. Mol Biotechnol. 2024. PMID: 39044064
-
Proteomics shows that brain metastases of lung adenocarcinoma overexpress ribosomal proteins in response to gamma knife radiosurgery.Sci Rep. 2024 Jul 8;14(1):15646. doi: 10.1038/s41598-024-58967-y. Sci Rep. 2024. PMID: 38977703 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous