Misplaced Pages

DNA repair-deficiency disorder

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
(Redirected from Inherited human DNA repair gene mutations that increase cancer risk) Medical condition
DNA repair-deficiency disorder
SpecialtyEndocrinology Edit this 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).
Protein Pathway Description
ATR Nucleotide excision repair 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
DNA-PKcs Non-homologous end joining shorter lifespan, earlier onset of aging related pathologies; higher level of DNA damage persistence
ERCC1 Nucleotide excision repair, Interstrand cross link repair deficient transcription coupled NER with time-dependent accumulation of transcription-blocking damages; mouse life span reduced from 2.5 years to 5 months;) Ercc1 mice are leukopenic and thrombocytopenic, and there is extensive adipose transformation of the bone marrow, hallmark features of normal aging in mice
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, intellectual disability, 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
ERCC4 (XPF) Nucleotide excision repair, Interstrand cross link repair, Single-strand annealing, Microhomology-mediated end joining 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, chronic kidney disease, muscle wasting, osteopenia, kyphosis and cerebral atrophy
ERCC5 (XPG) Nucleotide excision repair, Homologous recombinational repair, Base excision repair 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 premature aging features with shorter life span and photosensitivity, deficient transcription coupled NER with accumulation of unrepaired DNA damages, also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines
ERCC8 (Cockayne syndrome A or CS-A) Nucleotide excision repair premature aging features with shorter life span and photosensitivity, deficient transcription coupled NER with accumulation of unrepaired DNA damages, also defective repair of oxidatively generated DNA damages including 8-oxoguanine, 5-hydroxycytosine and cyclopurines
GTF2H5 (TTDA) Nucleotide excision repair deficiency causes trichothiodystrophy (TTD) a premature-ageing and neuroectodermal disease; humans with GTF2H5 mutations have a partially inactivated protein with retarded repair of 6-4-photoproducts
Ku70 Non-homologous end joining shorter lifespan, earlier onset of aging related pathologies; persistent foci of DNA double-strand break repair proteins
Ku80 Non-homologous end joining shorter lifespan, earlier onset of aging related pathologies; defective repair of spontaneous DNA damage
Lamin A Non-homologous end joining, Homologous recombination increased DNA damage and chromosome aberrations; progeria; aspects of premature aging; altered expression of numerous DNA repair factors
NRMT1 Nucleotide excision repair mutation in NRMT1 causes decreased body size, female-specific infertility, kyphosis, decreased mitochondrial function, and early-onset liver degeneration
RECQL4 Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining mutations in RECQL4 cause Rothmund-Thomson syndrome, with alopecia, sparse eyebrows and lashes, cataracts and osteoporosis
SIRT6 Base excision repair, Nucleotide excision repair, Homologous recombination, Non-homologous end joining SIRT6-deficient mice develop profound lymphopenia, loss of subcutaneous fat and lordokyphosis, and these defects overlap with aging-associated degenerative processes
SIRT7 Non-homologous end joining mice 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
Werner syndrome helicase Homologous recombination, Non-homologous end joining,Base excision repair, Replication arrest recovery shorter lifespan, earlier onset of aging related pathologies, genome instability
ZMPSTE24 Homologous recombination lack 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

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). 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"). 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". On the other hand, Cockayne Syndrome and trichothiodystrophy show mainly features of accelerated aging, but apparently without an increased risk of cancer Some DNA repair defects manifest as neurodegeneration rather than as cancer or "accelerated aging". (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.

Against this position other biogerontologists argue that premature aging phenotypes are identifiable symptoms associated with mechanisms of molecular damage. The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging". 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.

DNA repair defects and increased cancer risk

Individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer. 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 gene Protein Repair pathways affected Cancers with increased risk
breast cancer 1 & 2 BRCA1 BRCA2 HRR of double strand breaks and daughter strand gaps breast, ovarian
ataxia telangiectasia mutated ATM Different mutations in ATM reduce HRR, SSA or NHEJ leukemia, lymphoma, breast
Nijmegen breakage syndrome NBS (NBN) NHEJ lymphoid cancers
MRE11A MRE11 HRR and NHEJ breast
Bloom syndrome BLM (helicase) HRR leukemia, lymphoma, colon, breast, skin, lung, auditory canal, tongue, esophagus, stomach, tonsil, larynx, uterus
WRN WRN HRR, NHEJ, long patch BER soft tissue sarcoma, colorectal, skin, thyroid, pancreas
RECQL4 RECQ4 Helicase likely active in HRR basal cell carcinoma, squamous cell carcinoma, intraepidermal carcinoma
Fanconi anemia genes FANCA, B, C, D1, D2, E, F, G, I, J, L, M, N FANCA etc. HRR and TLS leukemia, liver tumors, solid tumors many areas
XPC, XPE (DDB2) XPC, XPE Global genomic NER, repairs damage in both transcribed and untranscribed DNA skin cancer (melanoma and non-melanoma)
XPA, XPB, XPD, XPF, XPG XPA XPB XPD XPF XPG Transcription coupled NER repairs the transcribed strands of transcriptionally active genes skin cancer (melanoma and non-melanoma)
XPV (also called polymerase H) XPV (POLH) Translesion synthesis (TLS) skin cancers (basal cell, squamous cell, melanoma)
mutS (E. coli) homolog 2, mutS (E. coli) homolog 6, mutL (E. coli) homolog 1,

postmeiotic segregation increased 2 (S. cerevisiae)

MSH2 MSH6 MLH1 PMS2 MMR colorectal, endometrial
mutY homolog (E. coli) MUTYH BER of A paired with 8-oxo-dG colon
TP53 P53 Direct role in HRR, BER, NER and acts in DNA damage response for those pathways and for NHEJ and MMR sarcomas, breast cancers, brain tumors, and adrenocortical carcinomas
NTHL1 NTHL1 BER for Tg, FapyG, 5-hC, 5-hU in dsDNA Colon cancer, endometrial cancer, duodenal cancer, basal-cell carcinoma

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): 1840. doi:10.3390/ijms17111840. PMC 5133840. PMID 27827925.
  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. doi:10.1016/j.stem.2007.03.002. PMC 2920603. PMID 18371340.
  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. doi:10.1038/sj.embor.7400127. PMC 1299048. PMID 15105825.
  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. Bibcode:2014PLoSO...993568R. doi:10.1371/journal.pone.0093568. PMC 3989187. PMID 24740260.
  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. doi:10.1016/j.freeradbiomed.2010.02.033. PMC 2901171. PMID 20193758.
  6. ^ Gregg SQ, Robinson AR, Niedernhofer LJ (2011). "Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease". DNA Repair (Amst.). 10 (7): 781–91. doi:10.1016/j.dnarep.2011.04.026. PMC 3139823. PMID 21612988.
  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. Bibcode:2016Natur.537..427V. doi:10.1038/nature19329. PMC 5161687. PMID 27556946.
  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: 7219. doi:10.3402/pba.v1i0.7219. PMC 3417667. PMID 22953029.
  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. doi:10.1016/j.dnarep.2011.04.028. PMC 3234290. PMID 21571596.
  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. doi:10.1128/MCB.24.6.2237-2242.2004. PMC 355871. 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. doi:10.1016/j.molcel.2015.12.026. PMC 4761302. PMID 26833090.
  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. doi:10.1093/nar/27.4.979. PMC 148276. 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 γ-irradiated human cells". Factors influencing the removal of thymine glycol from DNA in gamma-irradiated human cells. Progress in Nucleic Acid Research and Molecular Biology. Vol. 68. pp. 139–49. doi:10.1016/S0079-6603(01)68096-6. ISBN 9780125400688. PMID 11554293. {{cite book}}: |journal= ignored (help)
  14. ^ 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. doi:10.1016/j.jmb.2015.11.020. PMC 4738086. PMID 26616585.
  15. ^ 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. doi:10.1016/j.mad.2013.03.006. PMID 23562424. S2CID 25146054.
  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. doi:10.1371/journal.pgen.1003431. PMC 3630102. PMID 23637614.
  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. doi:10.1128/MCB.01462-10. PMC 3165551. PMID 21730288.
  18. ^ 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. doi:10.1016/j.mad.2007.08.006. PMC 2692937. PMID 17928034.
  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. doi:10.1007/s00412-016-0590-9. PMC 5371645. PMID 27136939.
  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. doi:10.1128/MCB.00785-07. PMC 2169178. PMID 17875923.
  21. Gonzalo S, Kreienkamp R (2016). "Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted Nuclear Lamina". The Nuclear Envelope. Methods in Molecular Biology. Vol. 1411. pp. 419–37. doi:10.1007/978-1-4939-3530-7_26. ISBN 978-1-4939-3528-4. PMC 5044759. PMID 27147057.
  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. doi:10.1074/jbc.M114.558510. PMC 4047379. PMID 24753253.
  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. doi:10.1016/j.mad.2015.03.012. PMC 4457563. PMID 25843235.
  24. ^ Lu L, Jin W, Wang LL (2017). "Aging in Rothmund-Thomson syndrome and related RECQL4 genetic disorders". Ageing Res. Rev. 33: 30–35. doi:10.1016/j.arr.2016.06.002. PMID 27287744. S2CID 28321025.
  25. Chalkiadaki A, Guarente L (2015). "The multifaceted functions of sirtuins in cancer". Nat. Rev. Cancer. 15 (10): 608–24. doi:10.1038/nrc3985. PMID 26383140. S2CID 3195442.
  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. doi:10.1016/j.cell.2005.11.044. PMID 16439206. S2CID 18517518.
  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. doi:10.15252/embj.201593499. PMC 4884211. PMID 27225932.
  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. doi:10.1128/mcb.22.20.6971-6978.2002. PMC 139822. 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. doi:10.1074/jbc.M114.578823. PMC 4175362. PMID 25122754.
  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. Bibcode:2016NatCo...713785S. doi:10.1038/ncomms13785. PMC 5150655. PMID 27922005.
  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. doi:10.1074/jbc.M703343200. PMID 17611195.
  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. doi:10.1093/nar/gks648. PMC 3458577. PMID 22753033.
  33. Pichierri P, Ammazzalorso F, Bignami M, Franchitto A (2011). "The Werner syndrome protein: linking the replication checkpoint response to genome stability". Aging. 3 (3): 311–8. doi:10.18632/aging.100293. PMC 3091524. PMID 21389352.
  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. doi:10.1016/j.dnarep.2009.12.011. PMC 2827637. PMID 20075015.
  35. Veith S, Mangerich A (2015). "RecQ helicases and PARP1 team up in maintaining genome integrity". Ageing Res. Rev. 23 (Pt A): 12–28. doi:10.1016/j.arr.2014.12.006. PMID 25555679. S2CID 29498397.
  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. doi:10.1038/nm1266. PMID 15980864. S2CID 11798376.
  37. ^ Best, BP (2009). "Nuclear DNA damage as a direct cause of aging" (PDF). Rejuvenation Research. 12 (3): 199–208. CiteSeerX 10.1.1.318.738. doi:10.1089/rej.2009.0847. PMID 19594328. Archived from the original (PDF) on 2017-11-15. Retrieved 2009-09-29.
  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. doi:10.1126/science.1079161. PMID 12610296. S2CID 840477.
  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. doi:10.1074/jbc.M111269200. PMID 11756455.
  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. doi:10.1016/j.cell.2007.08.043. PMID 17889645. S2CID 17615809.
  42. Miller RA (April 2004). "'Accelerated aging': a primrose path to insight?" (PDF). Aging Cell. 3 (2): 47–51. doi:10.1111/j.1474-9728.2004.00081.x. hdl:2027.42/73065. PMID 15038817. S2CID 41182844.
  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. doi:10.1111/j.1474-9728.2004.00082.x. PMID 15038819. S2CID 26832020.
  44. Hasty P, Vijg J (April 2004). "Rebuttal to Miller: 'Accelerated aging': a primrose path to insight?'". Aging Cell. 3 (2): 67–9. doi:10.1111/j.1474-9728.2004.00087.x. PMID 15038820. S2CID 26925937.
  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. doi:10.1016/j.dnarep.2007.02.020. PMC 2989184. PMID 17379580.
  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. doi:10.1016/j.ygyno.2014.09.009. PMID 25238946.
  48. ^ 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. doi:10.1096/fj.11-185546. PMID 21778326. S2CID 24698475.
  49. Thompson LH, Schild D (2002). "Recombinational DNA repair and human disease". Mutat. Res. 509 (1–2): 49–78. Bibcode:2002MRFMM.509...49T. doi:10.1016/s0027-5107(02)00224-5. PMID 12427531.
  50. ^ Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, Kalina MA, Digweed M (2012). "Nijmegen breakage syndrome (NBS)". Orphanet J Rare Dis. 7: 13. doi:10.1186/1750-1172-7-13. PMC 3314554. PMID 22373003.
  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. doi:10.1242/jcs.01355. PMID 15367581.
  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. doi:10.1016/j.molonc.2008.09.007. PMC 5527773. PMID 19383352.
  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. Bibcode:2008PNAS..10516906N. doi:10.1073/pnas.0809380105. PMC 2579351. PMID 18971343.
  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 1706430. PMID 5770175.
  55. Bohr VA (2005). "Deficient DNA repair in the human progeroid disorder, Werner syndrome". Mutat. Res. 577 (1–2): 252–9. Bibcode:2005MRFMM.577..252B. doi:10.1016/j.mrfmmm.2005.03.021. PMID 15916783.
  56. Monnat RJ (2010). "Human RECQ helicases: roles in DNA metabolism, mutagenesis and cancer biology". Semin. Cancer Biol. 20 (5): 329–39. doi:10.1016/j.semcancer.2010.10.002. PMC 3040982. PMID 20934517.
  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. doi:10.1007/s10522-008-9205-z. PMC 2713741. PMID 19083132.
  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 (378): 213–23. doi:10.1097/00003086-200009000-00032. PMID 10986997. S2CID 36781050.
  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. Bibcode:2009MRFMM.668...54T. doi:10.1016/j.mrfmmm.2009.02.003. PMC 2714807. PMID 19622404.
  60. Alter BP (2003). "Cancer in Fanconi anemia, 1927-2001". Cancer. 97 (2): 425–40. doi:10.1002/cncr.11046. PMID 12518367. S2CID 38251423.
  61. ^ Lehmann AR, McGibbon D, Stefanini M (2011). "Xeroderma pigmentosum". Orphanet J Rare Dis. 6: 70. doi:10.1186/1750-1172-6-70. PMC 3221642. PMID 22044607.
  62. ^ 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. doi:10.1111/j.1751-1097.2011.00909.x. PMC 3082610. PMID 21388382.
  63. ^ 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. doi:10.1590/s1415-47572014000200008. PMC 3983582. PMID 24764756.
  64. ^ 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. doi:10.1002/humu.22462. PMID 24130121. S2CID 2854418.
  65. ^ Meyer LA, Broaddus RR, Lu KH (2009). "Endometrial cancer and Lynch syndrome: clinical and pathologic considerations". Cancer Control. 16 (1): 14–22. doi:10.1177/107327480901600103. PMC 3693757. PMID 19078925.
  66. ^ Markkanen E, Dorn J, Hübscher U (2013). "MUTYH DNA glycosylase: the rationale for removing undamaged bases from the DNA". Front Genet. 4: 18. doi:10.3389/fgene.2013.00018. PMC 3584444. PMID 23450852.
  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. doi:10.1158/1541-7786.MCR-08-0020. PMID 18403632.
  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. doi:10.1016/j.bbrc.2005.03.192. PMID 15865943.
  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. doi:10.1200/EdBook_AM.2013.33.81. PMC 5889618. PMID 23714463.
  70. Krokan HE, Bjørås M (2013). "Base excision repair". Cold Spring Harb Perspect Biol. 5 (4): a012583. doi:10.1101/cshperspect.a012583. PMC 3683898. PMID 23545420.
  71. Kuiper RP, Hoogerbrugge N (2015). "NTHL1 defines novel cancer syndrome". Oncotarget. 6 (33): 34069–70. doi:10.18632/oncotarget.5864. PMC 4741436. PMID 26431160.

External links

ClassificationD
Congenital malformations and deformations of integument / skin disease
Genodermatosis
Congenital ichthyosis/
erythrokeratodermia
AD
AR
XR
Ungrouped
EB
and related
Ectodermal dysplasia
Elastic/Connective
Hyperkeratosis/
keratinopathy
PPK
Other
Other

see also Template:Congenital malformations and deformations of skin appendages, Template:Phakomatoses, Template:Pigmentation disorders, Template:DNA replication and repair-deficiency disorder

Developmental
anomalies
Midline
Nevus
Other/ungrouped
Categories: