Genome Integrity and Disease Prevention in the Nervous System

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2017 Aug 3

PMID 28765160

Citations 85

Authors

Peter J McKinnon

Affiliations

Soon will be listed here.

Abstract

Multiple DNA repair pathways maintain genome stability and ensure that DNA remains essentially unchanged over the life of a cell. Various human diseases occur if DNA repair is compromised, and most of these impact the nervous system, in some cases exclusively. However, it is often unclear what specific endogenous damage underpins disease pathology. Generally, the types of causative DNA damage are associated with replication, transcription, or oxidative metabolism; other direct sources of endogenous lesions may arise from aberrant topoisomerase activity or ribonucleotide incorporation into DNA. This review focuses on the etiology of DNA damage in the nervous system and the genome stability pathways that prevent human neurologic disease.

Citing Articles

Bioactivated Glucoraphanin Improves Cell Survival, Upregulating Phospho-AKT, and Modulates Genes Involved in DNA Repair in an In Vitro Alzheimer's Disease Model: A Network-Transcriptomic Analysis.

Minuti A, Mazzon E, Iori R, Chiricosta L, Artimagnella O Nutrients. 2024; 16(23).

PMID: 39683594 PMC: 11644231. DOI: 10.3390/nu16234202.

YIPF2 regulates genome integrity.

Zhang X, Wang T Cell Biosci. 2024; 14(1):114.

PMID: 39238039 PMC: 11376028. DOI: 10.1186/s13578-024-01300-x.

Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress.

De Jaime-Soguero A, Hattemer J, Bufe A, Haas A, van den Berg J, van Batenburg V Nat Commun. 2024; 15(1):7404.

PMID: 39191776 PMC: 11350214. DOI: 10.1038/s41467-024-51821-9.

Adaptive and Maladaptive DNA Breaks in Neuronal Physiology and Alzheimer's Disease.

Roberts A, Swerdlow R, Wang N Int J Mol Sci. 2024; 25(14).

PMID: 39063016 PMC: 11277458. DOI: 10.3390/ijms25147774.

Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders.

Kisby G, Wilson 3rd D, Spencer P Int J Mol Sci. 2024; 25(13).

PMID: 39000326 PMC: 11241460. DOI: 10.3390/ijms25137221.

References

Potenski C, Niu H, Sung P, Klein H . Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms. Nature. 2014; 511(7508):251-4. PMC: 4140095. DOI: 10.1038/nature13292. View

Seidle H, Bieganowski P, Brenner C . Disease-associated mutations inactivate AMP-lysine hydrolase activity of Aprataxin. J Biol Chem. 2005; 280(22):20927-31. PMC: 2556069. DOI: 10.1074/jbc.M502889200. View

Ginno P, Lott P, Christensen H, Korf I, Chedin F . R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol Cell. 2012; 45(6):814-25. PMC: 3319272. DOI: 10.1016/j.molcel.2012.01.017. View

Lieber M . The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010; 79:181-211. PMC: 3079308. DOI: 10.1146/annurev.biochem.052308.093131. View

Zhang J, Tripathi D, Jing J, Alexander A, Kim J, Powell R . ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat Cell Biol. 2015; 17(10):1259-1269. PMC: 4589490. DOI: 10.1038/ncb3230. View

Madabhushi R, Pan L, Tsai L . DNA damage and its links to neurodegeneration. Neuron. 2014; 83(2):266-282. PMC: 5564444. DOI: 10.1016/j.neuron.2014.06.034. View

Hill S, Mordes D, Cameron L, Neuberg D, Landini S, Eggan K . Two familial ALS proteins function in prevention/repair of transcription-associated DNA damage. Proc Natl Acad Sci U S A. 2016; 113(48):E7701-E7709. PMC: 5137757. DOI: 10.1073/pnas.1611673113. View

Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S . Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat Genet. 2001; 29(2):184-8. DOI: 10.1038/ng1001-184. View

Lee K, Padget K, Curtis H, Cowell I, Moiani D, Sondka Z . MRE11 facilitates the removal of human topoisomerase II complexes from genomic DNA. Biol Open. 2012; 1(9):863-73. PMC: 3507232. DOI: 10.1242/bio.20121834. View

10.

Gao Y, Sun Y, Frank K, Dikkes P, Fujiwara Y, Seidl K . A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell. 1999; 95(7):891-902. DOI: 10.1016/s0092-8674(00)81714-6. View

11.

Murga M, Bunting S, Montana M, Soria R, Mulero F, Canamero M . A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging. Nat Genet. 2009; 41(8):891-8. PMC: 2902278. DOI: 10.1038/ng.420. View

12.

Wardlaw C, Carr A, Oliver A . TopBP1: A BRCT-scaffold protein functioning in multiple cellular pathways. DNA Repair (Amst). 2014; 22:165-74. DOI: 10.1016/j.dnarep.2014.06.004. View

13.

De Bont R, Van Larebeke N . Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis. 2004; 19(3):169-85. DOI: 10.1093/mutage/geh025. View

14.

Katyal S, Lee Y, Nitiss K, Downing S, Li Y, Shimada M . Aberrant topoisomerase-1 DNA lesions are pathogenic in neurodegenerative genome instability syndromes. Nat Neurosci. 2014; 17(6):813-21. PMC: 4074009. DOI: 10.1038/nn.3715. View

15.

Williams G, Hammel M, Radhakrishnan S, Ramsden D, Lees-Miller S, Tainer J . Structural insights into NHEJ: building up an integrated picture of the dynamic DSB repair super complex, one component and interaction at a time. DNA Repair (Amst). 2014; 17:110-20. PMC: 4102006. DOI: 10.1016/j.dnarep.2014.02.009. View

16.

Bernstein N, Williams R, Rakovszky M, Cui D, Green R, Karimi-Busheri F . The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase. Mol Cell. 2005; 17(5):657-70. DOI: 10.1016/j.molcel.2005.02.012. View

17.

Enriquez-Rios V, Dumitrache L, Downing S, Li Y, Brown E, Russell H . DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis. J Neurosci. 2017; 37(4):893-905. PMC: 5296783. DOI: 10.1523/JNEUROSCI.4213-15.2016. View

18.

Reynolds J, Walker A, Gilmore E, Walsh C, Caldecott K . Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair. Nucleic Acids Res. 2012; 40(14):6608-19. PMC: 3413127. DOI: 10.1093/nar/gks318. View

19.

Sollier J, Cimprich K . Breaking bad: R-loops and genome integrity. Trends Cell Biol. 2015; 25(9):514-22. PMC: 4554970. DOI: 10.1016/j.tcb.2015.05.003. View

20.

Attwell D, Laughlin S . An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab. 2001; 21(10):1133-45. DOI: 10.1097/00004647-200110000-00001. View