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Translational Neurodegeneration
Published in: Translational Neurodegeneration 1/2019

Open Access 01-12-2019 | Review

DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria

Authors: Luis Bermúdez-Guzmán, Alejandro Leal

Published in: Translational Neurodegeneration | Issue 1/2019

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Abstract

Mutations in DNA repair enzymes can cause two neurological clinical manifestations: a developmental impairment and a degenerative disease. Polynucleotide kinase 3′-phosphatase (PNKP) is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems. Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum. Besides, mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration. Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system. As models, we analyze PNKP-related disorders, focusing on Charcot-Marie-Tooth disease and ataxia. A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases.
Literature
1.
2.
Leal A, Bogantes-Ledezma S, Ekici AB, Uebe S, Thiel CT, Sticht H, et al. The polynucleotide kinase 3′-phosphatase gene (PNKP) is involved in Charcot-Marie-tooth disease (CMT2B2) previously related to MED25. Neurogenetics. 2018;19:215–25.PubMedPubMedCentralCrossRef
3.
Bras J, Alonso I, Barbot C, Costa MM, Darwent L, Orme T, et al. Mutations in PNKP cause recessive Ataxia with oculomotor apraxia type 4. Am J Hum Genet. 2015;96:474–9.PubMedPubMedCentralCrossRef
4.
Breslin C, Caldecott KW. DNA 3′-phosphatase activity is critical for rapid global rates of single-Strand break repair following oxidative stress. Mol Cell Biol. 2009;29:4653–62.PubMedPubMedCentralCrossRef
5.
Reynolds JJ, Walker AK, Gilmore EC, Walsh CA, Caldecott KW. Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair. Nucleic Acids Res. 2012;40:6608–19.PubMedPubMedCentralCrossRef
6.
Weinfeld M, Mani RS, Abdou I, Aceytuno RD, Glover JNM. Tidying up loose ends: the role of polynucleotide kinase/phosphatase in DNA strand break repair. Trends Biochem Sci. 2011;36:262–71.PubMedPubMedCentralCrossRef
7.
Della-Maria J, Hegde ML, McNeill DR, Matsumoto Y, Tsai M-S, Ellenberger T, et al. The interaction between polynucleotide kinase phosphatase and the DNA repair protein XRCC1 is critical for repair of DNA alkylation damage and stable association at DNA damage sites. J Biol Chem. 2012;287:39233–44.PubMedPubMedCentralCrossRef
8.
Bernstein NK, Williams RS, Rakovszky ML, Cui D, Green R, Karimi-Busheri F, et al. The molecular architecture of the mammalian DNA repair enzyme, polynucleotide kinase. Mol Cell. 2005;17:657–70.PubMedCrossRef
9.
Audebert M, Salles B, Weinfeld M, Calsou P. Involvement of polynucleotide kinase in a poly(ADP-ribose) Polymerase-1-dependent DNA double-strand breaks rejoining pathway. J Mol Biol. 2006;356:257–65.PubMedCrossRef
10.
Barzilai A. The contribution of the DNA damage response to neuronal viability. Antioxid Redox Signal. 2007;9:211–8.PubMedCrossRef
11.
12.
Tann AW, Boldogh I, Meiss G, Qian W, Van Houten B, Mitra S, et al. Apoptosis induced by persistent single-strand breaks in mitochondrial genome: Critical role of exog (5′-Exo/Endonuclease) in their repair. J Biol Chem. 2011;286:31975–83.PubMedPubMedCentralCrossRef
13.
Narciso L, Parlanti E, Racaniello M, Simonelli V, Cardinale A, Merlo D, et al. The response to oxidative DNA damage in neurons: mechanisms and disease. Neural Plast. 2016;2016:1–14.CrossRef
14.
15.
Fortini P, Ferretti C, Dogliotti E. The response to DNA damage during differentiation: pathways and consequences. Mutat Res Mol Mech Mutagen. 2013;743–744:160–8.CrossRef
16.
Fortini P, Dogliotti E. Mechanisms of dealing with DNA damage in terminally differentiated cells. Mutat Res Mol Mech Mutagen. 2010;685:38–44.CrossRef
17.
Suberbielle E, Sanchez PE, Kravitz AV, Wang X, Ho K, Eilertson K, et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β. Nat Neurosci. 2013;16:613–21.PubMedPubMedCentralCrossRef
18.
Lieber MR, Ma Y, Pannicke U, Schwarz K. Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol. 2003;4:712–20.PubMedCrossRef
19.
Frank KM, Sharpless NE, Gao Y, Sekiguchi JM, Ferguson DO, Zhu C, et al. DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic lethality via the p53 pathway. Mol Cell. 2000;6:993–1002.CrossRef
20.
21.
22.
23.
24.
Shen J, Gilmore EC, Marshall CA, Haddadin M, Reynolds JJ, Eyaid W, et al. Mutations in PNKP cause microcephaly, seizures and defects in DNA repair. Nat Genet. 2010;42:245–9.PubMedPubMedCentralCrossRef
25.
Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary Ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42:174–83.PubMedCrossRef
26.
Gao R, Liu Y, Silva-Fernandes A, Fang X, Paulucci-Holthauzen A, Chatterjee A, et al. Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3. PLoS Genet. 2015;11:e1004834 Pearson CE, editor.PubMedPubMedCentralCrossRef
27.
Shimada M, Dumitrache LC, Russell HR, McKinnon PJ. Polynucleotide kinase-phosphatase enables neurogenesis via multiple DNA repair pathways to maintain genome stability. EMBO J. 2015;34:2465–80.PubMedPubMedCentralCrossRef
28.
Dumitrache LC, McKinnon PJ. Polynucleotide kinase-phosphatase (PNKP) mutations and neurologic disease. Mech Ageing Dev. 2017;161:121–9.PubMedCrossRef
29.
Aceytuno RD, Piett CG, Havali-Shahriari Z, Edwards RA, Rey M, Ye R, et al. Structural and functional characterization of the PNKP–XRCC4–LigIV DNA repair complex. Nucleic Acids Res. 2017;45:6238–51.PubMedPubMedCentralCrossRef
30.
Jiang B, Glover JNM, Weinfeld M. Neurological disorders associated with DNA strand-break processing enzymes. Mech Ageing Dev. 2017;161:130–40.PubMedCrossRef
31.
Chalasani SL, Kawale AS, Akopiants K, Yu Y, Fanta M, Weinfeld M, et al. Persistent 3′-phosphate termini and increased cytotoxicity of radiomimetic DNA double-strand breaks in cells lacking polynucleotide kinase/phosphatase despite presence of an alternative 3′-phosphatase. DNA Repair. 2018;68:12–24.PubMedCrossRefPubMedCentral
32.
Poulton C, Oegema R, Heijsman D, Hoogeboom J, Schot R, Stroink H, et al. Progressive cerebellar atrophy and polyneuropathy: expanding the spectrum of PNKP mutations. Neurogenetics. 2013;14:43–51.PubMedCrossRef
33.
Scholz C, Golas MM, Weber RG, Hartmann C, Lehmann U, Sahm F, et al. Rare compound heterozygous variants in PNKP identified by whole exome sequencing in a German patient with ataxia-oculomotor apraxia 4 and pilocytic astrocytoma. Clin Genet. 2018;94:185–6.PubMedCrossRef
34.
Carvill GL, Heavin SB, Yendle SC, McMahon JM, O’Roak BJ, Cook J, et al. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet. 2013;45:825–30.PubMedPubMedCentralCrossRef
35.
Mastrangelo M, Leuzzi V. Genes of early-onset epileptic encephalopathies: from genotype to phenotype. Pediatr Neurol. 2012;46:24–31.PubMedCrossRef
36.
Zsurka G, Kunz WS. Mitochondrial dysfunction and seizures: the neuronal energy crisis. Lancet Neurol. 2015;14:956–66.PubMedCrossRef
37.
Bindoff LA, Engelsen BA. Mitochondrial diseases and epilepsy: mitochondrial diseases and epilepsy. Epilepsia. 2012;53:92–7.PubMedCrossRef
38.
Sanganahalli BG, Herman P, Hyder F, Kannurpatti SS. Mitochondrial calcium uptake capacity modulates neocortical excitability. J Cereb Blood Flow Metab. 2013;33:1115–26.PubMedPubMedCentralCrossRef
39.
Pareyson D, Saveri P, Sagnelli A, Piscosquito G. Mitochondrial dynamics and inherited peripheral nerve diseases. Neurosci Lett. 2015;596:66–77.PubMedCrossRef
40.
Sajic M, Mastrolia V, Lee CY, Trigo D, Sadeghian M, Mosley AJ, et al. Impulse conduction increases mitochondrial transport in adult mammalian peripheral nerves in vivo. PLoS Biol. 2013;11:e1001754 Barres BA, editor.PubMedPubMedCentralCrossRef
41.
42.
43.
Ligon LA, Steward O. Movement of mitochondria in the axons and dendrites of cultured hippocampal neurons. J Comp Neurol. 2000;3:340–50.CrossRef
44.
45.
Parsons JL, Khoronenkova SV, Dianova II, Ternette N, Kessler BM, Datta PK, et al. Phosphorylation of PNKP by ATM prevents its proteasomal degradation and enhances resistance to oxidative stress. Nucleic Acids Res. 2012;40:11404–15.PubMedPubMedCentralCrossRef
46.
Nam DE, Yoo DH, Choi SS, Choi B-O, Chung KW. Wide phenotypic spectrum in axonal Charcot–Marie–tooth neuropathy type 2 patients with KIF5A mutations. Genes Genomics. 2018;40:77–84.PubMedCrossRef
47.
Goizet C, Boukhris A, Mundwiller E, Tallaksen C, Forlani S, Toutain A, et al. Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10. Hum Mutat. 2009;30:E376–85.PubMedCrossRef
48.
Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, et al. Mutations in the motor and stalk domains of KIF5A in spastic paraplegia type 10 and in axonal Charcot-Marie-tooth type 2. Clin Genet. 2012;82:157–64.PubMedCrossRef
49.
Campbell PD, Shen K, Sapio MR, Glenn TD, Talbot WS, Marlow FL. Unique function of kinesin Kif5A in localization of mitochondria in axons. J Neurosci. 2014;34:14717–32.PubMedPubMedCentralCrossRef
50.
Pareyson D, Marchesi C. Diagnosis, natural history, and management of Charcot–Marie–tooth disease. Lancet Neurol. 2009;8:654–67.PubMedCrossRef
51.
Cassereau J, Chevrollier A, Gueguen N, Desquiret V, Verny C, Nicolas G, et al. Mitochondrial dysfunction and pathophysiology of Charcot–Marie–tooth disease involving GDAP1 mutations. Exp Neurol. 2011;227:31–41.PubMedCrossRef
52.
Timmerman V, Clowes VE, Reid E. Overlapping molecular pathological themes link Charcot–Marie–tooth neuropathies and hereditary spastic paraplegias. Exp Neurol. 2013;246:14–25.PubMedCrossRef
53.
Noack R, Frede S, Albrecht P, Henke N, Pfeiffer A, Knoll K, et al. Charcot–Marie–tooth disease CMT4A: GDAP1 increases cellular glutathione and the mitochondrial membrane potential. Hum Mol Genet. 2012;21:150–62.PubMedCrossRef
54.
Niemann A, Huber N, Wagner KM, Somandin C, Horn M, Lebrun-Julien F, et al. The Gdap1 knockout mouse mechanistically links redox control to Charcot–Marie–tooth disease. Brain. 2014;137:668–82.PubMedPubMedCentralCrossRef
55.
Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH. Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci. 2010;30:4232–40.PubMedPubMedCentralCrossRef
56.
Misko AL, Sasaki Y, Tuck E, Milbrandt J, Baloh RH. Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration. J Neurosci. 2012;32:4145–55.PubMedPubMedCentralCrossRef
57.
Longley MJ, Graziewicz MA, Bienstock RJ, Copeland WC. Consequences of mutations in human DNA polymerase γ. Gene. 2005;354:125–31.PubMedCrossRef
58.
59.
60.
61.
Palau F, Estela A, Pla-Martín D, Sánchez-Piris M. The role of mitochondrial network dynamics in the pathogenesis of Charcot-Marie-tooth disease. Inherit Neuromuscul dis Transl Pathomechanisms Ther. 6th ed. Dordrecht: Springer Science+Business Media B.V; 2009. p. 129–37.
62.
63.
Mao P, Reddy PH. Is multiple sclerosis a mitochondrial disease? Biochim Biophys Acta (BBA) - Mol Basis Dis. 2010;1802:66–79.CrossRef
64.
Ashrafi G, Schlehe JS, LaVoie MJ, Schwarz TL. Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J Cell Biol. 2014;206:655–70.PubMedPubMedCentralCrossRef
65.
66.
67.
El-Khamisy SF. To live or to die: a matter of processing damaged DNA termini in neurons: DNA end processing and neurodegeneration. EMBO Mol Med. 2011;3:78–88.PubMedPubMedCentralCrossRef
68.
69.
Tahbaz N, Subedi S, Weinfeld M. Role of polynucleotide kinase/phosphatase in mitochondrial DNA repair. Nucleic Acids Res. 2012;40:3484–95.PubMedCrossRef
70.
Kazak L, Reyes A, Holt IJ. Minimizing the damage: repair pathways keep mitochondrial DNA intact. Nat Rev Mol Cell Biol. 2012;13:659–71.PubMedCrossRef
71.
Mandal SM, Hegde ML, Chatterjee A, Hegde PM, Szczesny B, Banerjee D, et al. Role of human DNA glycosylase Nei-like 2 (NEIL2) and single Strand break repair protein polynucleotide kinase 3′-phosphatase in maintenance of mitochondrial genome. J Biol Chem. 2012;287:2819–29.PubMedCrossRef
72.
Shokolenko I, Venediktova N, Bochkareva A, Wilson GL, Alexeyev MF. Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Res. 2009;37:2539–48.PubMedPubMedCentralCrossRef
73.
Alexeyev M, Shokolenko I, Wilson G, LeDoux S. The maintenance of mitochondrial DNA integrity--critical analysis and update. Cold Spring Harb Perspect Biol. 2013;5:a012641.PubMedPubMedCentralCrossRef
74.
75.
Wirtz S, Schuelke M. Region-specific expression of mitochondrial complex I genes during murine brain development. PLoS One. 2011;6:e18897 Feany MB, editor.PubMedPubMedCentralCrossRef
76.
Chakrabarti L, Zahra R, Jackson SM, Kazemi-Esfarjani P, Sopher BL, Mason AG, et al. Mitochondrial dysfunction in NnaD mutant flies and Purkinje cell degeneration mice reveals a role for Nna proteins in neuronal bioenergetics. Neuron. 2010;66:835–47.PubMedPubMedCentralCrossRef
77.
Girard M, Lariviere R, Parfitt DA, Deane EC, Gaudet R, Nossova N, et al. Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Proc Natl Acad Sci. 2012;109:1661–6.PubMedCrossRefPubMedCentral
78.
Gao Y, Katyal S, Lee Y, Zhao J, Rehg JE, Russell HR, et al. DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair. Nature. 2011;471:240–4.PubMedPubMedCentralCrossRef
79.
Murai J, Huang SN, Das BB, Dexheimer TS, Takeda S, Pommier Y. Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells. J Biol Chem. 2012;287:12848–57.PubMedPubMedCentralCrossRef
80.
81.
82.
83.
Katyal S, El-Khamisy SF, Russell HR, Li Y, Ju L, Caldecott KW, et al. TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. EMBO J. 2007;26:4720–31.PubMedPubMedCentralCrossRef
84.
Chiang S-C, Meagher M, Kassouf N, Hafezparast M, McKinnon PJ, Haywood R, et al. Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical–induced DNA damage. Sci Adv. 2017;3:e1602506.PubMedPubMedCentralCrossRef
85.
Ferro A, Carbone E, Zhang J, Marzouk E, Villegas M, Siegel A, et al. Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar ataxia type 1 (SCA1) mouse model. PLoS One. 2017;12:e0188425 Chakrabarti L, editor.PubMedPubMedCentralCrossRef
86.
Ripolone M, Lucchini V, Ronchi D, Fagiolari G, Bordoni A, Fortunato F, et al. Purkinje cell COX deficiency and mtDNA depletion in an animal model of spinocerebellar ataxia type 1. J Neurosci Res. 2018;96:1576–85.PubMedCrossRef
87.
Laço MN, Oliveira CR, Paulson HL, Rego AC. Compromised mitochondrial complex II in models of Machado–Joseph disease. Biochim Biophys Acta (BBA) - Mol Basis Dis. 2012;1822:139–49.CrossRef
88.
Chou A-H, Yeh T-H, Kuo Y-L, Kao Y-C, Jou M-J, Hsu C-Y, et al. Polyglutamine-expanded ataxin-3 activates mitochondrial apoptotic pathway by upregulating Bax and downregulating Bcl-xL. Neurobiol Dis. 2006;21:333–45.PubMedCrossRef
89.
Goti D. A mutant Ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration. J Neurosci. 2004;24:10266–79.PubMedCrossRefPubMedCentral
90.
91.
Tzoulis C, Tran GT, Coxhead J, Bertelsen B, Lilleng PK, Balafkan N, et al. Molecular pathogenesis of polymerase gamma-related neurodegeneration: POLG-related neurodegeneration. Ann Neurol. 2014;76:66–81.PubMedPubMedCentralCrossRef
92.
Abeti R, Parkinson MH, Hargreaves IP, Angelova PR, Sandi C, Pook MA, et al. Mitochondrial energy imbalance and lipid peroxidation cause cell death in Friedreich’s ataxia. Cell Death Dis. 2016;7:e2237.PubMedPubMedCentralCrossRef
93.
Chiang S, Kovacevic Z, Sahni S, Lane DJR, Merlot AM, Kalinowski DS, et al. Frataxin and the molecular mechanism of mitochondrial iron-loading in Friedreich’s ataxia. Clin Sci. 2016;130:853–70.CrossRef
94.
Choi M, Kipps T, Kurzrock R. ATM mutations in Cancer: therapeutic implications. Mol Cancer Ther. 2016;15:1781–91.PubMedCrossRef
95.
Chow H-M, Cheng A, Song X, Swerdel MR, Hart RP, Herrup K. ATM is activated by ATP depletion and modulates mitochondrial function through NRF1. J Cell Biol. 2019;218:909–28.PubMedCrossRefPubMedCentral
96.
Zhang Y, Lee J-H, Paull TT, Gehrke S, D’Alessandro A, Dou Q, et al. Mitochondrial redox sensing by the kinase ATM maintains cellular antioxidant capacity. Sci Signal. 2018;11:eaaq0702.PubMedPubMedCentralCrossRef
97.
Valentin-Vega YA, Maclean KH, Tait-Mulder J, Milasta S, Steeves M, Dorsey FC, et al. Mitochondrial dysfunction in ataxia-telangiectasia. Blood. 2012;119:1490–500.PubMedPubMedCentralCrossRef
98.
Fang EF, Scheibye-Knudsen M, Brace LE, Kassahun H, SenGupta T, Nilsen H, et al. Defective Mitophagy in XPA via PARP-1 Hyperactivation and NAD+/SIRT1 reduction. Cell. 2014;157:882–96.PubMedPubMedCentralCrossRef
99.
Manandhar M, Lowery MG, Boulware KS, Lin KH, Lu Y, Wood RD. Transcriptional consequences of XPA disruption in human cell lines. DNA Repair. 2017;57:76–90.PubMedPubMedCentralCrossRef
100.
Scheibye-Knudsen M, Fang EF, Croteau DL, Bohr VA. Contribution of defective mitophagy to the neurodegeneration in DNA repair-deficient disorders. Autophagy. 2014;10:1468–9.PubMedPubMedCentralCrossRef
101.
Hoch NC, Hanzlikova H, Rulten SL, Tétreault M, Komulainen E, Ju L, et al. XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature. 2017;541:87–91.PubMedCrossRef
102.
Fang EF, Scheibye-Knudsen M, Chua KF, Mattson MP, Croteau DL, Bohr VA. Nuclear DNA damage signalling to mitochondria in ageing. Nat Rev Mol Cell Biol. 2016;17:308–21.PubMedPubMedCentralCrossRef
103.
Shull ERP, Lee Y, Nakane H, Stracker TH, Zhao J, Russell HR, et al. Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS. Genes Dev. 2009;23:171–80.PubMedPubMedCentralCrossRef
104.
Lee Y, Katyal S, Li Y, El-Khamisy SF, Russell HR, Caldecott KW, et al. The genesis of cerebellar interneurons and the prevention of neural DNA damage require XRCC1. Nat Neurosci. 2009;12:973–80.PubMedPubMedCentralCrossRef
Metadata
Title
DNA repair deficiency in neuropathogenesis: when all roads lead to mitochondria
Authors
Luis Bermúdez-Guzmán
Alejandro Leal
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Translational Neurodegeneration / Issue 1/2019
Electronic ISSN: 2047-9158
DOI
https://doi.org/10.1186/s40035-019-0156-x

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