DNA damage foci: Meaning and significance
- PMID: 25773265
- DOI: 10.1002/em.21944
DNA damage foci: Meaning and significance
Abstract
The discovery of DNA damage response proteins such as γH2AX, ATM, 53BP1, RAD51, and the MRE11/RAD50/NBS1 complex, that accumulate and/or are modified in the vicinity of a chromosomal DNA double-strand break to form microscopically visible, subnuclear foci, has revolutionized the detection of these lesions and has enabled studies of the cellular machinery that contributes to their repair. Double-strand breaks are induced directly by a number of physical and chemical agents, including ionizing radiation and radiomimetic drugs, but can also arise as secondary lesions during replication and DNA repair following exposure to a wide range of genotoxins. Here we aim to review the biological meaning and significance of DNA damage foci, looking specifically at a range of different settings in which such markers of DNA damage and repair are being studied and interpreted.
Keywords: 53BP1; DNA double-strand break; genotoxicity; ionizing radiation; γH2AX.
© 2015 Wiley Periodicals, Inc.
Similar articles
-
γH2AX foci on apparently intact mitotic chromosomes: not signatures of misrejoining events but signals of unresolved DNA damage.Cell Cycle. 2014;13(19):3026-36. doi: 10.4161/15384101.2014.947786. Cell Cycle. 2014. PMID: 25486563 Free PMC article.
-
Double strand break repair functions of histone H2AX.Mutat Res. 2013 Oct;750(1-2):5-14. doi: 10.1016/j.mrfmmm.2013.07.007. Epub 2013 Jul 31. Mutat Res. 2013. PMID: 23916969 Free PMC article. Review.
-
Replication protein A and gamma-H2AX foci assembly is triggered by cellular response to DNA double-strand breaks.Exp Cell Res. 2004 Nov 1;300(2):320-34. doi: 10.1016/j.yexcr.2004.07.022. Exp Cell Res. 2004. PMID: 15474997
-
Distinct kinetics of DNA repair protein accumulation at DNA lesions and cell cycle-dependent formation of γH2AX- and NBS1-positive repair foci.Biol Cell. 2015 Dec;107(12):440-54. doi: 10.1111/boc.201500050. Epub 2015 Nov 17. Biol Cell. 2015. PMID: 26482424
-
Use of γH2AX and other biomarkers of double-strand breaks during radiotherapy.Semin Radiat Oncol. 2010 Oct;20(4):223-31. doi: 10.1016/j.semradonc.2010.05.004. Semin Radiat Oncol. 2010. PMID: 20832014 Review.
Cited by
-
A multi-functional role for the MCM8/9 helicase complex in maintaining fork integrity during replication stress.Nat Commun. 2022 Aug 30;13(1):5090. doi: 10.1038/s41467-022-32583-8. Nat Commun. 2022. PMID: 36042199 Free PMC article.
-
FEN1 endonuclease as a therapeutic target for human cancers with defects in homologous recombination.Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19415-19424. doi: 10.1073/pnas.2009237117. Epub 2020 Jul 27. Proc Natl Acad Sci U S A. 2020. PMID: 32719125 Free PMC article.
-
Ultra-short laser-accelerated proton pulses have similar DNA-damaging effectiveness but produce less immediate nitroxidative stress than conventional proton beams.Sci Rep. 2016 Aug 31;6:32441. doi: 10.1038/srep32441. Sci Rep. 2016. PMID: 27578260 Free PMC article.
-
Field size effects on DNA damage and proliferation in normal human cell populations irradiated with X-ray microbeams.Sci Rep. 2021 Mar 26;11(1):7001. doi: 10.1038/s41598-021-86416-7. Sci Rep. 2021. PMID: 33772061 Free PMC article.
-
TET1 regulates DNA repair in human glial cells.Toxicol Appl Pharmacol. 2019 Oct 1;380:114646. doi: 10.1016/j.taap.2019.114646. Epub 2019 Jul 3. Toxicol Appl Pharmacol. 2019. PMID: 31278917 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous