Close menu

DNA repair-deficiency disorder


Source: http://en.wikipedia.org/wiki/DNA_repair-deficiency_disorder
Updated: 2017-06-16T00:37Z
DNA repair-deficiency disorder
Classification and external resources
Specialty{{#statements:P1995}}
Patient UKDNA repair-deficiency disorder
MeSHD049914
[[[d:Lua error in Module:Wikidata at line 1009: attempt to index field 'wikibase' (a nil value).|edit on Wikidata]]]

A DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.

DNA repair defects can cause an accelerated aging disease or an increased risk of cancer, or sometimes both.

DNA repair defects and accelerated aging

DNA repair defects are seen in nearly all of the diseases described as accelerated aging disease, in which various tissues, organs or systems of the human body age prematurely. Because the accelerated aging diseases display different aspects of aging, but never every aspect, they are often called segmental progerias by biogerontologists.

Human disorders with accelerated aging

Examples

Some examples of DNA repair defects causing progeroid syndromes in humans or mice are shown in Table 1.

Table 1. DNA repair proteins that, when deficient, cause features of accelerated aging (segmental progeria).
ProteinPathwayDescription
ATRNucleotide excision repair[1]deletion of ATR in adult mice leads to a number of disorders including hair loss and graying, kyphosis, osteoporosis, premature involution of the thymus, fibrosis of the heart and kidney and decreased spermatogenesis[2]
DNA-PKcsNon-homologous end joiningshorter lifespan, earlier onset of aging related pathologies;[3][4] higher level of DNA damage persistence[5]
ERCC1Nucleotide excision repair, Interstrand cross link repair[6]deficient transcription coupled NER with time-dependent accumulation of transcription-blocking damages;[7] mouse life span reduced from 2.5 years to 5 months;[8]) Ercc1−/− mice are leukopenic and thrombocytopenic, and there is extensive adipose transformation of the bone marrow, hallmark features of normal aging in mice[6]
ERCC2 (XPD)Nucleotide excision repair (also transcription as part of TFIIH)some mutations in ERCC2 cause Cockayne syndrome in which patients have segmental progeria with reduced stature, mental retardation, cachexia (loss of subcutaneous fat tissue), sensorineural deafness, retinal degeneration, and calcification of the central nervous system; other mutations in ERCC2 cause trichothiodystrophy in which patients have segmental progeria with brittle hair, short stature, progressive cognitive impairment and abnormal face shape; still other mutations in ERCC2 cause xeroderma pigmentosum (without a progeroid syndrome) and with extreme sun-mediated skin cancer predisposition[9]
ERCC4 (XPF)Nucleotide excision repair, Interstrand cross link repair, Single-strand annealing, Microhomology-mediated end joining[6]mutations in ERCC4 cause symptoms of accelerated aging that affect the neurologic, hepatobiliary, musculoskeletal, and hematopoietic systems, and cause an old, wizened appearance, loss of subcutaneous fat, liver dysfunction, vision and hearing loss, renal insufficiency, muscle wasting, osteopenia, kyphosis and cerebral atrophy[6]
ERCC5 (XPG)Nucleotide excision repair,[10] Homologous recombinational repair,[11] Base excision repair[12][13]mice with deficient ERCC5 show loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4-5 months
ERCC6 (Cockayne syndrome B or CS-B)Nucleotide excision repair [especially transcription coupled repair (TC-NER) and interstrand crosslink repair]premature aging features with shorter life span and photosensitivity,[14] deficient transcription coupled NER with accumulation of unrepaired DNA damages,[15] also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines[15]
ERCC8 (Cockayne syndrome A or CS-A)Nucleotide excision repair [especially transcription coupled repair (TC-NER) and interstrand crosslink repair]premature aging features with shorter life span and photosensitivity,[14] deficient transcription coupled NER with accumulation of unrepaired DNA damages,[15] also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines[15]
GTF2H5 (TTDA)Nucleotide excision repairdeficiency causes trichothiodystrophy (TTD) a premature-ageing and neuroectodermal disease; humans with GTF2H5 mutations have a partially inactivated protein[16] with retarded repair of 6-4-photoproducts[17]
Ku70Non-homologous end joiningshorter lifespan, earlier onset of aging related pathologies;[18] persistent foci of DNA double-strand break repair proteins[19]
Ku80Non-homologous end joiningshorter lifespan, earlier onset of aging related pathologies;[20] defective repair of spontaneous DNA damage[18]
Lamin ANon-homologous end joining, Homologous recombinationincreased DNA damage and chromosome aberrations; progeria; aspects of premature aging; altered expression of numerous DNA repair factors[21]
NRMT1Nucleotide excision repair[22]mutation in NRMT1 causes decreased body size, female-specific infertility, kyphosis, decreased mitochondrial function, and early-onset liver degeneration[23]
RECQL4Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining[24]mutations in RECQL4 cause Rothmund-Thomson syndrome, with alopecia, sparse eye brows and lashes, cataracts and osteoporosis[24]
SIRT6Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining [25]SIRT6-deficient mice develop profound lymphopenia, loss of subcutaneous fat and lordokyphosis, and these defects overlap with aging-associated degenerative processes[26]
SIRT7Non-homologous end joiningmice defective in SIRT7 show phenotypic and molecular signs of accelerated aging such as premature pronounced curvature of the spine, reduced life span, and reduced non-homologous end joining[27]
Werner syndrome helicaseHomologous recombination,[28][29] Non-homologous end joining,[30]Base excision repair,[31][32] Replication arrest recovery[33]shorter lifespan, earlier onset of aging related pathologies, genome instability[34][35]
ZMPSTE24Homologous recombinationlack of Zmpste24 prevents lamin A formation and causes progeroid phenotypes in mice and humans, increased DNA damage and chromosome aberrations, sensitivity to DNA-damaging agents and deficiency in homologous recombination[36]

DNA repair defects distinguished from "accelerated aging"

Most of the DNA repair deficiency diseases show varying degrees of "accelerated aging" or cancer (often some of both).[37] But elimination of any gene essential for base excision repair kills the embryo—it is too lethal to display symptoms (much less symptoms of cancer or "accelerated aging").[38] Rothmund-Thomson syndrome and xeroderma pigmentosum display symptoms dominated by vulnerability to cancer, whereas progeria and Werner syndrome show the most features of "accelerated aging". Hereditary nonpolyposis colorectal cancer (HNPCC) is very often caused by a defective MSH2 gene leading to defective mismatch repair, but displays no symptoms of "accelerated aging".[39] On the other hand, Cockayne Syndrome and trichothiodystrophy show mainly features of accelerated aging, but apparently without an increased risk of cancer[40] Some DNA repair defects manifest as neurodegeneration rather than as cancer or "accelerated aging".[41] (Also see the "DNA damage theory of aging" for a discussion of the evidence that DNA damage is the primary underlying cause of aging.)

Debate concerning "accelerated aging"

Some biogerontologists question that such a thing as "accelerated aging" actually exists, at least partly on the grounds that all of the so-called accelerated aging diseases are segmental progerias. Many disease conditions such as diabetes, high blood pressure, etc., are associated with increased mortality. Without reliable biomarkers of aging it is hard to support the claim that a disease condition represents more than accelerated mortality.[42]

Against this position other biogerontologists argue that premature aging phenotypes are identifiable symptoms associated with mechanisms of molecular damage.[37] The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging".[43] Such conditions, it is argued, are readily distinguishable from genetic diseases associated with increased mortality, but not associated with an aging phenotype, such as cystic fibrosis and sickle cell anemia. It is further argued that segmental aging phenotype is a natural part of aging insofar as genetic variation leads to some people being more disposed than others to aging-associated diseases such as cancer and Alzheimer's disease.[44]

DNA repair defects and increased cancer risk

Individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer.[45] When a mutation is present in a DNA repair gene, the repair gene will either not be expressed or be expressed in an altered form. Then the repair function will likely be deficient, and, as a consequence, damages will tend to accumulate. Such DNA damages can cause errors during DNA synthesis leading to mutations, some of which may give rise to cancer. Germ-line DNA repair mutations that increase the risk of cancer are listed in the Table.

Inherited DNA repair gene mutations that increase cancer risk
DNA repair geneProteinRepair pathways affectedCancers with increased risk
breast cancer 1 & 2BRCA1 BRCA2HRR of double strand breaks and daughter strand gaps[46]breast, ovarian [47]
ataxia telangiectasia mutatedATMDifferent mutations in ATM reduce HRR, SSA or NHEJ [48]leukemia, lymphoma, breast [48][49]
Nijmegen breakage syndromeNBS (NBN)NHEJ [50]lymphoid cancers [50]
MRE11AMRE11HRR and NHEJ [51]breast [52]
Bloom syndromeBLM (helicase)HRR [53]leukemia, lymphoma, colon, breast, skin, lung, auditory canal, tongue, esophagus, stomach, tonsil, larynx, uterus [54]
WRNWRNHRR, NHEJ, long patch BER [55]soft tissue sarcoma, colorectal, skin, thyroid, pancreas [56]
RECQL4RECQ4Helicase likely active in HRR [57]basal cell carcinoma, squamous cell carcinoma, intraepidermal carcinoma [58]
Fanconi anemia genes FANCA,B,C,D1,D2,E,F,G,I,J,L,M,NFANCA etc.HRR and TLS [59]leukemia, liver tumors, solid tumors many areas [60]
XPC, XPE (DDB2)XPC, XPEGlobal genomic NER, repairs damage in both transcribed and untranscribed DNA [61][62]skin cancer (melanoma and non-melanoma) [61][62]
XPA, XPB, XPD, XPF, XPGXPA XPB XPD XPF XPGTranscription coupled NER repairs the transcribed strands of transcriptionally active genes [63]skin cancer (melanoma and non-melanoma) [63]
XPV (also called polymerase H)XPV (POLH)Translesion synthesis (TLS) [64]skin cancers (basal cell, squamous cell, melanoma) [64]
mutS (E. coli) homolog 2, mutS (E. coli) homolog 6, mutL (E. coli) homolog 1,

postmeiotic segregation increased 2 (S. cerevisiae)

MSH2 MSH6 MLH1 PMS2MMR [65]colorectal, endometrial [65]
mutY homolog (E. coli)MUTYHBER of A paired with 8-oxo-dG [66]colon [66]
TP53P53Direct role in HRR, BER, NER and acts in DNA damage response[67] for those pathways and for NHEJ and MMR [68]sarcomas, breast cancers, brain tumors, and adrenocortical carcinomas [69]
NTHL1NTHL1BER for Tg, FapyG, 5-hC, 5-hU in dsDNA[70]Colon cancer, endometrial cancer, duodenal cancer, basal-cell carcinoma[71]

See also

References

  1. ^ Park JM, Kang TH (2016). "Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation". Int J Mol Sci. 17 (11). PMC 5133840Freely accessible. PMID 27827925. doi:10.3390/ijms17111840. 
  2. ^ Ruzankina Y, Pinzon-Guzman C, Asare A, Ong T, Pontano L, Cotsarelis G, Zediak VP, Velez M, Bhandoola A, Brown EJ (2007). "Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss". Cell Stem Cell. 1 (1): 113–26. PMC 2920603Freely accessible. PMID 18371340. doi:10.1016/j.stem.2007.03.002. 
  3. ^ Espejel S, Martín M, Klatt P, Martín-Caballero J, Flores JM, Blasco MA (2004). "Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice". EMBO Rep. 5 (5): 503–9. PMC 1299048Freely accessible. PMID 15105825. doi:10.1038/sj.embor.7400127. 
  4. ^ Reiling E, Dollé ME, Youssef SA, Lee M, Nagarajah B, Roodbergen M, de With P, de Bruin A, Hoeijmakers JH, Vijg J, van Steeg H, Hasty P (2014). "The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency". PLoS ONE. 9 (4): e93568. PMC 3989187Freely accessible. PMID 24740260. doi:10.1371/journal.pone.0093568. 
  5. ^ Peddi P, Loftin CW, Dickey JS, Hair JM, Burns KJ, Aziz K, Francisco DC, Panayiotidis MI, Sedelnikova OA, Bonner WM, Winters TA, Georgakilas AG (2010). "DNA-PKcs deficiency leads to persistence of oxidatively induced clustered DNA lesions in human tumor cells". Free Radic. Biol. Med. 48 (10): 1435–43. PMC 2901171Freely accessible. PMID 20193758. doi:10.1016/j.freeradbiomed.2010.02.033. 
  6. ^ a b c d Gregg SQ, Robinson AR, Niedernhofer LJ (2011). "Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease". DNA Repair (Amst.). 10 (7): 781–91. PMC 3139823Freely accessible. PMID 21612988. doi:10.1016/j.dnarep.2011.04.026. 
  7. ^ Vermeij WP, Dollé ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis Á, Pothof J, Vijg J, van Steeg H, Hoeijmakers JH (2016). "Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice". Nature. 537 (7620): 427–431. PMC 5161687Freely accessible. PMID 27556946. doi:10.1038/nature19329. 
  8. ^ Dollé ME, Kuiper RV, Roodbergen M, Robinson J, de Vlugt S, Wijnhoven SW, Beems RB, de la Fonteyne L, de With P, van der Pluijm I, Niedernhofer LJ, Hasty P, Vijg J, Hoeijmakers JH, van Steeg H (2011). "Broad segmental progeroid changes in short-lived Ercc1(-/Δ7) mice". Pathobiol Aging Age Relat Dis. 1. PMC 3417667Freely accessible. PMID 22953029. doi:10.3402/pba.v1i0.7219. 
  9. ^ Fuss JO, Tainer JA (2011). "XPB and XPD helicases in TFIIH orchestrate DNA duplex opening and damage verification to coordinate repair with transcription and cell cycle via CAK kinase". DNA Repair (Amst.). 10 (7): 697–713. PMC 3234290Freely accessible. PMID 21571596. doi:10.1016/j.dnarep.2011.04.028. 
  10. ^ Tian M, Jones DA, Smith M, Shinkura R, Alt FW (2004). "Deficiency in the nuclease activity of xeroderma pigmentosum G in mice leads to hypersensitivity to UV irradiation". Mol. Cell. Biol. 24 (6): 2237–42. PMC 355871Freely accessible. PMID 14993263. 
  11. ^ Trego KS, Groesser T, Davalos AR, Parplys AC, Zhao W, Nelson MR, Hlaing A, Shih B, Rydberg B, Pluth JM, Tsai MS, Hoeijmakers JH, Sung P, Wiese C, Campisi J, Cooper PK (2016). "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability". Mol. Cell. 61 (4): 535–46. PMC 4761302Freely accessible. PMID 26833090. doi:10.1016/j.molcel.2015.12.026. 
  12. ^ Bessho T (1999). "Nucleotide excision repair 3' endonuclease XPG stimulates the activity of base excision repair enzyme thymine glycol DNA glycosylase". Nucleic Acids Res. 27 (4): 979–83. PMC 148276Freely accessible. PMID 9927729. 
  13. ^ Weinfeld M, Xing JZ, Lee J, Leadon SA, Cooper PK, Le XC (2001). "Factors influencing the removal of thymine glycol from DNA in gamma-irradiated human cells". Prog. Nucleic Acid Res. Mol. Biol. 68: 139–49. PMID 11554293. 
  14. ^ a b Iyama T, Wilson DM (2016). "Elements That Regulate the DNA Damage Response of Proteins Defective in Cockayne Syndrome". J. Mol. Biol. 428 (1): 62–78. PMC 4738086Freely accessible. PMID 26616585. doi:10.1016/j.jmb.2015.11.020. 
  15. ^ a b c d D'Errico M, Pascucci B, Iorio E, Van Houten B, Dogliotti E (2013). "The role of CSA and CSB protein in the oxidative stress response". Mech. Ageing Dev. 134 (5-6): 261–9. PMID 23562424. doi:10.1016/j.mad.2013.03.006. 
  16. ^ Theil AF, Nonnekens J, Steurer B, Mari PO, de Wit J, Lemaitre C, Marteijn JA, Raams A, Maas A, Vermeij M, Essers J, Hoeijmakers JH, Giglia-Mari G, Vermeulen W (2013). "Disruption of TTDA results in complete nucleotide excision repair deficiency and embryonic lethality". PLoS Genet. 9 (4): e1003431. PMC 3630102Freely accessible. PMID 23637614. doi:10.1371/journal.pgen.1003431. 
  17. ^ Theil AF, Nonnekens J, Wijgers N, Vermeulen W, Giglia-Mari G (2011). "Slowly progressing nucleotide excision repair in trichothiodystrophy group A patient fibroblasts". Mol. Cell. Biol. 31 (17): 3630–8. PMC 3165551Freely accessible. PMID 21730288. doi:10.1128/MCB.01462-10. 
  18. ^ a b Holcomb VB, Vogel H, Hasty P (2007). "Deletion of Ku80 causes early aging independent of chronic inflammation and Rag-1-induced DSBs". Mech. Ageing Dev. 128 (11-12): 601–8. PMC 2692937Freely accessible. PMID 17928034. doi:10.1016/j.mad.2007.08.006. 
  19. ^ Ahmed EA, Vélaz E, Rosemann M, Gilbertz KP, Scherthan H (2017). "DNA repair kinetics in SCID mice Sertoli cells and DNA-PKcs-deficient mouse embryonic fibroblasts". Chromosoma. 126 (2): 287–298. PMC 5371645Freely accessible. PMID 27136939. doi:10.1007/s00412-016-0590-9. 
  20. ^ Li H, Vogel H, Holcomb VB, Gu Y, Hasty P (2007). "Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer". Mol. Cell. Biol. 27 (23): 8205–14. PMC 2169178Freely accessible. PMID 17875923. doi:10.1128/MCB.00785-07. 
  21. ^ Gonzalo S, Kreienkamp R (2016). "Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted Nuclear Lamina". Methods Mol. Biol. 1411: 419–37. PMC 5044759Freely accessible. PMID 27147057. doi:10.1007/978-1-4939-3530-7_26. 
  22. ^ Cai Q, Fu L, Wang Z, Gan N, Dai X, Wang Y (2014). "α-N-methylation of damaged DNA-binding protein 2 (DDB2) and its function in nucleotide excision repair". J. Biol. Chem. 289 (23): 16046–56. PMC 4047379Freely accessible. PMID 24753253. doi:10.1074/jbc.M114.558510. 
  23. ^ Bonsignore LA, Tooley JG, Van Hoose PM, Wang E, Cheng A, Cole MP, Schaner Tooley CE (2015). "NRMT1 knockout mice exhibit phenotypes associated with impaired DNA repair and premature aging". Mech. Ageing Dev. 146-148: 42–52. PMC 4457563Freely accessible. PMID 25843235. doi:10.1016/j.mad.2015.03.012. 
  24. ^ a b Lu L, Jin W, Wang LL (2017). "Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders". Ageing Res. Rev. 33: 30–35. PMID 27287744. doi:10.1016/j.arr.2016.06.002. 
  25. ^ Chalkiadaki A, Guarente L (2015). "The multifaceted functions of sirtuins in cancer". Nat. Rev. Cancer. 15 (10): 608–24. PMID 26383140. doi:10.1038/nrc3985. 
  26. ^ Mostoslavsky, R; Chua, KF; Lombard, DB; Pang, WW; Fischer, MR; Gellon, L; Liu, P; Mostoslavsky, G; Franco, S; Murphy, MM; Mills, KD; Patel, P; Hsu, JT; Hong, AL; Ford, E; Cheng, HL; Kennedy, C; Nunez, N; Bronson, R; Frendewey, D; Auerbach, W; Valenzuela, D; Karow, M; Hottiger, MO; Hursting, S; Barrett, JC; Guarente, L; Mulligan, R; Demple, B; Yancopoulos, GD; Alt, FW (Jan 2006). "Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell. 124 (2): 315–29. PMID 16439206. doi:10.1016/j.cell.2005.11.044. 
  27. ^ Vazquez BN, Thackray JK, Simonet NG, Kane-Goldsmith N, Martinez-Redondo P, Nguyen T, Bunting S, Vaquero A, Tischfield JA, Serrano L (2016). "SIRT7 promotes genome integrity and modulates non-homologous end joining DNA repair". EMBO J. 35 (14): 1488–503. PMC 4884211Freely accessible. PMID 27225932. doi:10.15252/embj.201593499. 
  28. ^ Saintigny Y, Makienko K, Swanson C, Emond MJ, Monnat RJ (2002). "Homologous recombination resolution defect in werner syndrome". Mol. Cell. Biol. 22 (20): 6971–8. PMC 139822Freely accessible. PMID 12242278. 
  29. ^ Sturzenegger A, Burdova K, Kanagaraj R, Levikova M, Pinto C, Cejka P, Janscak P (2014). "DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells". J. Biol. Chem. 289 (39): 27314–26. PMC 4175362Freely accessible. PMID 25122754. doi:10.1074/jbc.M114.578823. 
  30. ^ Shamanna RA, Lu H, de Freitas JK, Tian J, Croteau DL, Bohr VA (2016). "WRN regulates pathway choice between classical and alternative non-homologous end joining". Nat Commun. 7: 13785. PMC 5150655Freely accessible. PMID 27922005. doi:10.1038/ncomms13785. 
  31. ^ Das A, Boldogh I, Lee JW, Harrigan JA, Hegde ML, Piotrowski J, de Souza Pinto N, Ramos W, Greenberg MM, Hazra TK, Mitra S, Bohr VA (2007). "The human Werner syndrome protein stimulates repair of oxidative DNA base damage by the DNA glycosylase NEIL1". J. Biol. Chem. 282 (36): 26591–602. PMID 17611195. doi:10.1074/jbc.M703343200. 
  32. ^ Kanagaraj R, Parasuraman P, Mihaljevic B, van Loon B, Burdova K, König C, Furrer A, Bohr VA, Hübscher U, Janscak P (2012). "Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage". Nucleic Acids Res. 40 (17): 8449–59. PMC 3458577Freely accessible. PMID 22753033. doi:10.1093/nar/gks648. 
  33. ^ Pichierri P, Ammazzalorso F, Bignami M, Franchitto A (2011). "The Werner syndrome protein: linking the replication checkpoint response to genome stability". Aging (Albany NY). 3 (3): 311–8. PMC 3091524Freely accessible. PMID 21389352. doi:10.18632/aging.100293. 
  34. ^ Rossi ML, Ghosh AK, Bohr VA (2010). "Roles of Werner syndrome protein in protection of genome integrity". DNA Repair (Amst.). 9 (3): 331–44. PMC 2827637Freely accessible. PMID 20075015. doi:10.1016/j.dnarep.2009.12.011. 
  35. ^ Veith S, Mangerich A (2015). "RecQ helicases and PARP1 team up in maintaining genome integrity". Ageing Res. Rev. 23 (Pt A): 12–28. PMID 25555679. doi:10.1016/j.arr.2014.12.006. 
  36. ^ Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ, Pei D, Pendas AM, Cadiñanos J, López-Otín C, Tse HF, Hutchison C, Chen J, Cao Y, Cheah KS, Tryggvason K, Zhou Z (2005). "Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780–5. PMID 15980864. doi:10.1038/nm1266. 
  37. ^ a b Best,BP (2009). "Nuclear DNA damage as a direct cause of aging" (PDF). Rejuvenation Research. 12 (3): 199–208. PMID 19594328. doi:10.1089/rej.2009.0847. 
  38. ^ Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J (February 2003). "Aging and genome maintenance: lessons from the mouse?". Science. 299 (5611): 1355–9. PMID 12610296. doi:10.1126/science.1079161. 
  39. ^ Mazurek A, Berardini M, Fishel R (March 2002). "Activation of human MutS homologs by 8-oxo-guanine DNA damage". J. Biol. Chem. 277 (10): 8260–6. PMID 11756455. doi:10.1074/jbc.M111269200. 
  40. ^ Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009 Oct 8;361(15):1475-85.
  41. ^ Rass U, Ahel I, West SC (September 2007). "Defective DNA repair and neurodegenerative disease". Cell. 130 (6): 991–1004. PMID 17889645. doi:10.1016/j.cell.2007.08.043. 
  42. ^ Miller RA (April 2004). "'Accelerated aging': a primrose path to insight?". Aging Cell. 3 (2): 47–51. PMID 15038817. doi:10.1111/j.1474-9728.2004.00081.x. 
  43. ^ Hasty P, Vijg J (April 2004). "Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity". Aging Cell. 3 (2): 55–65. PMID 15038819. doi:10.1111/j.1474-9728.2004.00082.x. 
  44. ^ Hasty P, Vijg J (April 2004). "Rebuttal to Miller: 'Accelerated aging': a primrose path to insight?'". Aging Cell. 3 (2): 67–9. PMID 15038820. doi:10.1111/j.1474-9728.2004.00087.x. 
  45. ^ Bernstein C, Bernstein H, Payne CM, Garewal H. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat Res. 2002 Jun;511(2):145-78. Review.
  46. ^ Nagaraju G, Scully R (2007). "Minding the gap: the underground functions of BRCA1 and BRCA2 at stalled replication forks". DNA Repair (Amst.). 6 (7): 1018–31. PMC 2989184Freely accessible. PMID 17379580. doi:10.1016/j.dnarep.2007.02.020. 
  47. ^ Lancaster JM, Powell CB, Chen LM, Richardson DL (2015). "Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions". Gynecol. Oncol. 136 (1): 3–7. PMID 25238946. doi:10.1016/j.ygyno.2014.09.009. 
  48. ^ a b Keimling M, Volcic M, Csernok A, Wieland B, Dörk T, Wiesmüller L (2011). "Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of specific DNA double-strand break-repair signaling pathways". FASEB J. 25 (11): 3849–60. PMID 21778326. doi:10.1096/fj.11-185546. 
  49. ^ Thompson LH, Schild D (2002). "Recombinational DNA repair and human disease". Mutat. Res. 509 (1-2): 49–78. PMID 12427531. doi:10.1016/s0027-5107(02)00224-5. 
  50. ^ a b Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M (2012). "Nijmegen breakage syndrome (NBS)". Orphanet J Rare Dis. 7: 13. PMC 3314554Freely accessible. PMID 22373003. doi:10.1186/1750-1172-7-13. 
  51. ^ Rapp A, Greulich KO (2004). "After double-strand break induction by UV-A, homologous recombination and nonhomologous end joining cooperate at the same DSB if both systems are available". J. Cell. Sci. 117 (Pt 21): 4935–45. PMID 15367581. doi:10.1242/jcs.01355. 
  52. ^ Bartkova J, Tommiska J, Oplustilova L, Aaltonen K, Tamminen A, Heikkinen T, Mistrik M, Aittomäki K, Blomqvist C, Heikkilä P, Lukas J, Nevanlinna H, Bartek J (2008). "Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene". Mol Oncol. 2 (4): 296–316. PMID 19383352. doi:10.1016/j.molonc.2008.09.007. 
  53. ^ Nimonkar AV, Ozsoy AZ, Genschel J, Modrich P, Kowalczykowski SC (2008). "Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair". Proc. Natl. Acad. Sci. U.S.A. 105 (44): 16906–11. PMC 2579351Freely accessible. PMID 18971343. doi:10.1073/pnas.0809380105. 
  54. ^ German J (1969). "Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients". Am. J. Hum. Genet. 21 (2): 196–227. PMC 1706430Freely accessible. PMID 5770175. 
  55. ^ Bohr VA (2005). "Deficient DNA repair in the human progeroid disorder, Werner syndrome". Mutat. Res. 577 (1-2): 252–9. PMID 15916783. doi:10.1016/j.mrfmmm.2005.03.021. 
  56. ^ Monnat RJ (2010). "Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology". Semin. Cancer Biol. 20 (5): 329–39. PMC 3040982Freely accessible. PMID 20934517. doi:10.1016/j.semcancer.2010.10.002. 
  57. ^ Singh DK, Ahn B, Bohr VA (2009). "Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging". Biogerontology. 10 (3): 235–52. PMC 2713741Freely accessible. PMID 19083132. doi:10.1007/s10522-008-9205-z. 
  58. ^ Anbari KK, Ierardi-Curto LA, Silber JS, Asada N, Spinner N, Zackai EH, Belasco J, Morrissette JD, Dormans JP (2000). "Two primary osteosarcomas in a patient with Rothmund-Thomson syndrome". Clin. Orthop. Relat. Res. 378: 213–23. PMID 10986997. doi:10.1097/00003086-200009000-00032. 
  59. ^ Thompson LH, Hinz JM (2009). "Cellular and molecular consequences of defective Fanconi anemia proteins in replication-coupled DNA repair: mechanistic insights". Mutat. Res. 668 (1-2): 54–72. PMC 2714807Freely accessible. PMID 19622404. doi:10.1016/j.mrfmmm.2009.02.003. 
  60. ^ Alter BP (2003). "Cancer in Fanconi anemia, 1927-2001". Cancer. 97 (2): 425–40. PMID 12518367. doi:10.1002/cncr.11046. 
  61. ^ a b Lehmann AR, McGibbon D, Stefanini M (2011). "Xeroderma pigmentosum". Orphanet J Rare Dis. 6: 70. PMC 3221642Freely accessible. PMID 22044607. doi:10.1186/1750-1172-6-70. 
  62. ^ a b Oh KS, Imoto K, Emmert S, Tamura D, DiGiovanna JJ, Kraemer KH (2011). "Nucleotide excision repair proteins rapidly accumulate but fail to persist in human XP-E (DDB2 mutant) cells". Photochem. Photobiol. 87 (3): 729–33. PMC 3082610Freely accessible. PMID 21388382. doi:10.1111/j.1751-1097.2011.00909.x. 
  63. ^ a b Menck CF, Munford V (2014). "DNA repair diseases: What do they tell us about cancer and aging?". Genet. Mol. Biol. 37 (1 Suppl): 220–33. PMC 3983582Freely accessible. PMID 24764756. doi:10.1590/s1415-47572014000200008. 
  64. ^ a b Opletalova K, Bourillon A, Yang W, Pouvelle C, Armier J, Despras E, Ludovic M, Mateus C, Robert C, Kannouche P, Soufir N, Sarasin A (2014). "Correlation of phenotype/genotype in a cohort of 23 xeroderma pigmentosum-variant patients reveals 12 new disease-causing POLH mutations". Hum. Mutat. 35 (1): 117–28. PMID 24130121. doi:10.1002/humu.22462. 
  65. ^ a b Meyer LA, Broaddus RR, Lu KH (2009). "Endometrial cancer and Lynch syndrome: clinical and pathologic considerations". Cancer Control. 16 (1): 14–22. PMC 3693757Freely accessible. PMID 19078925. 
  66. ^ a b Markkanen E, Dorn J, Hübscher U (2013). "MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA". Front Genet. 4: 18. PMC 3584444Freely accessible. PMID 23450852. doi:10.3389/fgene.2013.00018. 
  67. ^ Kastan MB (2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol. Cancer Res. 6 (4): 517–24. PMID 18403632. doi:10.1158/1541-7786.MCR-08-0020. 
  68. ^ Viktorsson K, De Petris L, Lewensohn R (2005). "The role of p53 in treatment responses of lung cancer". Biochem. Biophys. Res. Commun. 331 (3): 868–80. PMID 15865943. doi:10.1016/j.bbrc.2005.03.192. 
  69. ^ Testa JR, Malkin D, Schiffman JD (2013). "Connecting molecular pathways to hereditary cancer risk syndromes". Am Soc Clin Oncol Educ Book. 33: 81–90. PMID 23714463. doi:10.1200/EdBook_AM.2013.33.81. 
  70. ^ Krokan HE, Bjørås M (2013). "Base excision repair". Cold Spring Harb Perspect Biol. 5 (4): a012583. PMC 3683898Freely accessible. PMID 23545420. doi:10.1101/cshperspect.a012583. 
  71. ^ Kuiper RP, Hoogerbrugge N (2015). "NTHL1 defines novel cancer syndrome". Oncotarget. 6 (33): 34069–70. PMC 4741436Freely accessible. PMID 26431160. doi:10.18632/oncotarget.5864. 

External links

Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.

Also On Wow