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== A MMEJ no cancro ==
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[[FEN1]] is over-expressed in the majority of cancers of the breast,<ref name=Singh>{{cite journal |vauthors=Singh P, Yang M, Dai H, Yu D, Huang Q, Tan W, Kernstine KH, Lin D, Shen B |title=Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers |journal=Mol. Cancer Res. |volume=6 |issue=11 |pages=1710–7 |year=2008 |pmid=19010819 |pmc=2948671 |doi=10.1158/1541-7786.MCR-08-0269 |url=}}</ref> prostate,<ref name="pmid16879693">{{cite journal |vauthors=Lam JS, Seligson DB, Yu H, Li A, Eeva M, Pantuck AJ, Zeng G, Horvath S, Belldegrun AS |title=Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score |journal=BJU Int. |volume=98 |issue=2 |pages=445–51 |year=2006 |pmid=16879693 |doi=10.1111/j.1464-410X.2006.06224.x |url=}}</ref> stomach,<ref name="pmid15701830">{{cite journal |vauthors=Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, Kim JH, Song KS, Rho SM, Yoo HS, Yoo HS, Kim YS, Kim JG, Kim NS |title=Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells |journal=Clin. Cancer Res. |volume=11 |issue=2 Pt 1 |pages=473–82 |year=2005 |pmid=15701830 |doi= |url=}}</ref><ref name="pmid24590400">{{cite journal |vauthors=Wang K, Xie C, Chen D |title=Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis |journal=Int. J. Mol. Med. |volume=33 |issue=5 |pages=1268–74 |year=2014 |pmid=24590400 |doi=10.3892/ijmm.2014.1682 |url=}}</ref> neuroblastomas,<ref name="pmid15922863">{{cite journal |vauthors=Krause A, Combaret V, Iacono I, Lacroix B, Compagnon C, Bergeron C, Valsesia-Wittmann S, Leissner P, Mougin B, Puisieux A |title=Genome-wide analysis of gene expression in neuroblastomas detected by mass screening |journal=Cancer Lett. |volume=225 |issue=1 |pages=111–20 |year=2005 |pmid=15922863 |doi=10.1016/j.canlet.2004.10.035 |url=}}</ref> pancreatic,<ref name="pmid12651607">{{cite journal |vauthors=Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, Walter K, Sato N, Parker A, Ashfaq R, Jaffee E, Ryu B, Jones J, Eshleman JR, Yeo CJ, Cameron JL, Kern SE, Hruban RH, Brown PO, Goggins M |title=Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays |journal=Am. J. Pathol. |volume=162 |issue=4 |pages=1151–62 |year=2003 |pmid=12651607 |pmc=1851213 |doi=10.1016/S0002-9440(10)63911-9 |url=}}</ref> and lung.<ref name="pmid19596913">{{cite journal |vauthors=Nikolova T, Christmann M, Kaina B |title=FEN1 is overexpressed in testis, lung and brain tumors |journal=Anticancer Res. |volume=29 |issue=7 |pages=2453–9 |year=2009 |pmid=19596913 |doi= |url=}}</ref> ▼
▲[[FEN1]] isestá over-expressedsobreexpresado inna themaioría majoritydos ofcancros cancersde of the breastmama,<ref name=Singh>{{cite journal |vauthors=Singh P, Yang M, Dai H, Yu D, Huang Q, Tan W, Kernstine KH, Lin D, Shen B |title=Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers |journal=Mol. Cancer Res. |volume=6 |issue=11 |pages=1710–7 |year=2008 |pmid=19010819 |pmc=2948671 |doi=10.1158/1541-7786.MCR-08-0269 |url=}}</ref> prostate,<ref name="pmid16879693">{{cite journal |vauthors=Lam JS, Seligson DB, Yu H, Li A, Eeva M, Pantuck AJ, Zeng G, Horvath S, Belldegrun AS |title=Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score |journal=BJU Int. |volume=98 |issue=2 |pages=445–51 |year=2006 |pmid=16879693 |doi=10.1111/j.1464-410X.2006.06224.x |url=}}</ref> stomachestómago,<ref name="pmid15701830">{{cite journal |vauthors=Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, Kim JH, Song KS, Rho SM, Yoo HS, Yoo HS, Kim YS, Kim JG, Kim NS |title=Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells |journal=Clin. Cancer Res. |volume=11 |issue=2 Pt 1 |pages=473–82 |year=2005 |pmid=15701830 |doi= |url=}}</ref><ref name="pmid24590400">{{cite journal |vauthors=Wang K, Xie C, Chen D |title=Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis |journal=Int. J. Mol. Med. |volume=33 |issue=5 |pages=1268–74 |year=2014 |pmid=24590400 |doi=10.3892/ijmm.2014.1682 |url=}}</ref> neuroblastomas,<ref name="pmid15922863">{{cite journal |vauthors=Krause A, Combaret V, Iacono I, Lacroix B, Compagnon C, Bergeron C, Valsesia-Wittmann S, Leissner P, Mougin B, Puisieux A |title=Genome-wide analysis of gene expression in neuroblastomas detected by mass screening |journal=Cancer Lett. |volume=225 |issue=1 |pages=111–20 |year=2005 |pmid=15922863 |doi=10.1016/j.canlet.2004.10.035 |url=}}</ref> pancreaticpancreático,<ref name="pmid12651607">{{cite journal |vauthors=Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, Walter K, Sato N, Parker A, Ashfaq R, Jaffee E, Ryu B, Jones J, Eshleman JR, Yeo CJ, Cameron JL, Kern SE, Hruban RH, Brown PO, Goggins M |title=Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays |journal=Am. J. Pathol. |volume=162 |issue=4 |pages=1151–62 |year=2003 |pmid=12651607 |pmc=1851213 |doi=10.1016/S0002-9440(10)63911-9 |url=}}</ref> and lung.<ref name="pmid19596913">{{cite journal |vauthors=Nikolova T, Christmann M, Kaina B |title=FEN1 is overexpressed in testis, lung and brain tumors |journal=Anticancer Res. |volume=29 |issue=7 |pages=2453–9 |year=2009 |pmid=19596913 |doi= |url=}}</ref>
[[LIG3|Ligase III]] is upregulated in chronic myeloid leukemia,<ref name="pmid18524993">{{cite journal |vauthors=Sallmyr A, Tomkinson AE, Rassool FV |title=Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks |journal=Blood |volume=112 |issue=4 |pages=1413–23 |year=2008 |pmid=18524993 |pmc=2967309 |doi=10.1182/blood-2007-07-104257 |url=}}</ref> multiple myeloma,<ref name="pmid25790254">{{cite journal |vauthors=Herrero AB, San Miguel J, Gutierrez NC |title=Deregulation of DNA double-strand break repair in multiple myeloma: implications for genome stability |journal=PLoS ONE |volume=10 |issue=3 |pages=e0121581 |year=2015 |pmid=25790254 |pmc=4366222 |doi=10.1371/journal.pone.0121581 |url=}}</ref> and breast cancer.<ref name="pmid22112941">{{cite journal |vauthors=Tobin LA, Robert C, Nagaria P, Chumsri S, Twaddell W, Ioffe OB, Greco GE, Brodie AH, Tomkinson AE, Rassool FV |title=Targeting abnormal DNA repair in therapy-resistant breast cancers |journal=Mol. Cancer Res. |volume=10 |issue=1 |pages=96–107 |year=2012 |pmid=22112941 |pmc=3319138 |doi=10.1158/1541-7786.MCR-11-0255 |url=}}</ref> ▼
▲A [[LIG3|Ligase III]] isestá upregulatedregulada iná chronicalza myeloidna leukemialeucemia mieloide crónica,<ref name="pmid18524993">{{cite journal |vauthors=Sallmyr A, Tomkinson AE, Rassool FV |title=Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks |journal=Blood |volume=112 |issue=4 |pages=1413–23 |year=2008 |pmid=18524993 |pmc=2967309 |doi=10.1182/blood-2007-07-104257 |url=}}</ref> multiplemieloma myelomamúltiple,<ref name="pmid25790254">{{cite journal |vauthors=Herrero AB, San Miguel J, Gutierrez NC |title=Deregulation of DNA double-strand break repair in multiple myeloma: implications for genome stability |journal=PLoS ONE |volume=10 |issue=3 |pages=e0121581 |year=2015 |pmid=25790254 |pmc=4366222 |doi=10.1371/journal.pone.0121581 |url=}}</ref> ande cancro breastde cancermama.<ref name="pmid22112941">{{cite journal |vauthors=Tobin LA, Robert C, Nagaria P, Chumsri S, Twaddell W, Ioffe OB, Greco GE, Brodie AH, Tomkinson AE, Rassool FV |title=Targeting abnormal DNA repair in therapy-resistant breast cancers |journal=Mol. Cancer Res. |volume=10 |issue=1 |pages=96–107 |year=2012 |pmid=22112941 |pmc=3319138 |doi=10.1158/1541-7786.MCR-11-0255 |url=}}</ref>
[[MRE11A|MRE11]] is over-expressed in breast cancers.<ref name="pmid22914783">{{cite journal |vauthors=Yuan SS, Hou MF, Hsieh YC, Huang CY, Lee YC, Chen YJ, Lo S |title=Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer |journal=J. Natl. Cancer Inst. |volume=104 |issue=19 |pages=1485–502 |year=2012 |pmid=22914783 |doi=10.1093/jnci/djs355 |url=}}</ref> ▼
▲[[MRE11A|MRE11]] issobreesprésased over-expresseden incancros breastde cancersmama.<ref name="pmid22914783">{{cite journal |vauthors=Yuan SS, Hou MF, Hsieh YC, Huang CY, Lee YC, Chen YJ, Lo S |title=Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer |journal=J. Natl. Cancer Inst. |volume=104 |issue=19 |pages=1485–502 |year=2012 |pmid=22914783 |doi=10.1093/jnci/djs355 |url=}}</ref>
[[Nibrin|NBS1]] is over-expressed in some prostate cancers,<ref name="pmid25415046">{{cite journal |vauthors=Berlin A, Lalonde E, Sykes J, Zafarana G, Chu KC, Ramnarine VR, Ishkanian A, Sendorek DH, Pasic I, Lam WL, Jurisica I, van der Kwast T, Milosevic M, Boutros PC, Bristow RG |title=NBN gain is predictive for adverse outcome following image-guided radiotherapy for localized prostate cancer |journal=Oncotarget |volume=5 |issue=22 |pages=11081–90 |year=2014 |pmid=25415046 |pmc=4294365 |doi= 10.18632/oncotarget.2404|url=}}</ref> in head and neck cancer,<ref name="pmid16428493">{{cite journal |vauthors=Yang MH, Chiang WC, Chou TY, Chang SY, Chen PM, Teng SC, Wu KJ |title=Increased NBS1 expression is a marker of aggressive head and neck cancer and overexpression of NBS1 contributes to transformation |journal=Clin. Cancer Res. |volume=12 |issue=2 |pages=507–15 |year=2006 |pmid=16428493 |doi=10.1158/1078-0432.CCR-05-1231 |url=}}</ref> and in squamous cell carcinoma of the oral cavity.<ref name="pmid20175780">{{cite journal |vauthors=Hsu DS, Chang SY, Liu CJ, Tzeng CH, Wu KJ, Kao JY, Yang MH |title=Identification of increased NBS1 expression as a prognostic marker of squamous cell carcinoma of the oral cavity |journal=Cancer Sci. |volume=101 |issue=4 |pages=1029–37 |year=2010 |pmid=20175780 |doi=10.1111/j.1349-7006.2009.01471.x |url=}}</ref>
A [[PARP1Nibrina|NBS1]] isestá over-expressedsobreexpresado innalgúns tyrosinecancros kinase-activatedde leukemiaspróstata,<ref name="pmid25828893pmid25415046">{{cite journal |vauthors=MuvarakBerlin NA, KelleyLalonde SE, RobertSykes CJ, BaerZafarana MRG, PerrottiChu DKC, Gambacorti-PasseriniRamnarine CVR, CivinIshkanian CA, ScheibnerSendorek KDH, RassoolPasic FV |title=c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ FactorsI, LIG3 andLam PARP1WL, inJurisica Tyrosine Kinase-Activated Leukemias |journal=Mol. Cancer Res. |volume=13 |issue=4 |pages=699–712 |year=2015 |pmid=25828893 |doi=10.1158/1541-7786.MCR-14-0422 |url= |pmc=4398615}}</ref> in neuroblastomaI,<ref name="pmid25563294">{{citevan journalder |vauthors=NewmanKwast EAT, LuMilosevic FM, BashllariBoutros DPC, WangBristow L, Opipari AW, Castle VPRG |title=AlternativeNBN NHEJgain Pathwayis Componentspredictive Arefor Therapeuticadverse Targetsoutcome infollowing Highimage-Riskguided radiotherapy for Neuroblastomalocalized prostate cancer |journal=Mol. Cancer Res.Oncotarget |volume=135 |issue=322 |pages=470–8211081–90 |year=20152014 |pmid=2556329425415046 |pmc=4294365 |doi= 10.115818632/1541-7786oncotarget.MCR-14-0337 2404|url=}}</ref> inen testicularcancro andde othercabeza germ celle tumorspescozo,<ref name="pmid23486608pmid16428493">{{cite journal |vauthors=MegoYang MMH, CiernaChiang ZWC, SvetlovskaChou DTY, MacakChang DSY, MachalekovaChen KPM, MiskovskaTeng VSC, ChovanecWu M,KJ Usakova|title=Increased V,NBS1 Obertovaexpression J,is Babala P,marker Mardiakof Jaggressive |title=PARPhead expressionand inneck germcancer celland overexpression of NBS1 contributes to tumourstransformation |journal=J. Clin. PatholCancer Res. |volume=6612 |issue=72 |pages=607–12507–15 |year=20132006 |pmid=2348660816428493 |doi=10.11361158/jclinpath1078-20120432.CCR-20108805-1231 |url=}}</ref> and in Ewing’ssquamous sarcoma,cell carcinoma of the oral cavity.<ref name="pmid11956622pmid20175780">{{cite journal |vauthors=NewmanHsu REDS, SoldatenkovChang VASY, DritschiloLiu ACJ, NotarioTzeng VCH, Wu KJ, Kao JY, Yang MH |title=Poly(ADP-ribose)Identification polymeraseof turnoverincreased alterationsNBS1 doexpression notas contributea toprognostic PARPmarker overexpressionof insquamous Ewing'scell sarcomacarcinoma cellsof the oral cavity |journal=Oncol.Cancer RepSci. |volume=9101 |issue=34 |pages=529–321029–37 |year=20022010 |pmid=1195662220175780 |doi= 10.38921111/orj.91349-7006.32009.52901471.x |url=}}</ref>
[[XRCC1PARP1]] isestá over-expressedsobreexpresado innas [[non-small-cellleucemias lungactivadas carcinoma]]por (NSCLC)tirosina quinase,<ref name=Kang"pmid25828893">{{cite journal |vauthors=KangMuvarak CHN, JangKelley BGS, KimRobert DWC, ChungBaer DHMR, KimPerrotti YTD, JheonGambacorti-Passerini SC, SungCivin SWC, KimScheibner JHK, Rassool FV |title=Thec-MYC prognosticGenerates significanceRepair ofErrors ERCC1,via BRCA1,Increased XRCC1,Transcription andof betaIIIAlternative-tubulinNHEJ expressionFactors, inLIG3 patientsand withPARP1, non-small cell lung cancer treatedin byTyrosine platinumKinase-Activated and taxane-based neoadjuvant chemotherapy and surgical resectionLeukemias |journal=LungMol. Cancer Res. |volume=6813 |issue=34 |pages=478–83699–712 |year=20102015 |pmid=1968382625828893 |doi=10.10161158/j1541-7786.lungcan.2009.07.004MCR-14-0422 |url= |pmc=4398615}}</ref> anden at an even higher level in metastatic lymph nodes of NSCLC.neuroblastoma,<ref name="pmid25563294">{{cite journal |vauthors=KangNewman CHEA, JangLu BGF, KimBashllari DWD, ChungWang DHL, KimOpipari YTAW, JheonCastle S, Sung SW, Kim JHVP |title=DifferencesAlternative inNHEJ thePathway expressionComponents profilesAre of excision repair crosscomplementation group 1, x-ray repair crosscomplementation group 1, and betaIII-tubulin between primary non-small cell lung cancer and metastatic lymph nodes and theTherapeutic significanceTargets in midHigh-termRisk survivalNeuroblastoma |journal=JMol. ThoracCancer OncolRes. |volume=413 |issue=113 |pages=1307–12470–82 |year=20092015 |pmid=1974576625563294 |doi=10.10971158/JTO1541-7786.0b013e3181b9f236MCR-14-0337 |url=}}</ref> en Perhapstumors eventesticulares moree interesting, '''deficiency''' inde [[XRCC1liña xerminal|células xerminais]],<ref duename="pmid23486608">{{cite tojournal being [[Zygosity#heterozygous|heterozygous]]vauthors=Mego forM, aCierna mutatedZ, XRCC1Svetlovska geneD, codingMacak forD, aMachalekova truncatedK, XRCC1Miskovska proteinV, suppressesChovanec tumorM, growthUsakova inV, miceObertova J, Babal P, Mardiak J |title=PARP expression in threegerm experimentalcell conditionstumours for|journal=J. inducingClin. threePathol. types|volume=66 of|issue=7 cancer|pages=607–12 (colon|year=2013 cancer,|pmid=23486608 melanoma|doi=10.1136/jclinpath-2012-201088 or|url=}}</ref> breaste cancer)no sarcoma de Ewing.<ref name=Pettan-Brewer"pmid11956622">{{cite journal |vauthors=Pettan-BrewerNewman CRE, MortonSoldatenkov JVA, CullenDritschilo SA, EnnsNotario L,V Kehrli|title=Poly(ADP-ribose) KR,polymerase Sidorovaturnover J,alterations Gohdo J,not Coilcontribute R,to LadigesPARP WC |title=Tumor growth is suppressedoverexpression in miceEwing's expressingsarcoma a truncated XRCC1 proteincells |journal=AmOncol. J Cancer ResRep. |volume=29 |issue=23 |pages=168–77529–32 |year=20122002 |pmid=22432057 |pmc=330457111956622 |doi= |url=10.3892/or.9.3.529}}</ref>
[[XRCC1]] sobreexprésase no carcinoma de pulmón de células non pequenas,<ref name=Kang>{{cite journal |vauthors=Kang CH, Jang BG, Kim DW, Chung DH, Kim YT, Jheon S, Sung SW, Kim JH |title=The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection |journal=Lung Cancer |volume=68 |issue=3 |pages=478–83 |year=2010 |pmid=19683826 |doi=10.1016/j.lungcan.2009.07.004 |url=}}</ref> e nun nivel aínda maior nos [[ganglio linfático|ganglios linfáticos]] non metastáticos do carcinoma de pulmón de células non pequenas.<ref>{{cite journal |vauthors=Kang CH, Jang BG, Kim DW, Chung DH, Kim YT, Jheon S, Sung SW, Kim JH |title=Differences in the expression profiles of excision repair crosscomplementation group 1, x-ray repair crosscomplementation group 1, and betaIII-tubulin between primary non-small cell lung cancer and metastatic lymph nodes and the significance in mid-term survival |journal=J Thorac Oncol |volume=4 |issue=11 |pages=1307–12 |year=2009 |pmid=19745766 |doi=10.1097/JTO.0b013e3181b9f236 |url=}}</ref> A '''deficiencia''' en [[XRCC1]], debida a ser [[cigosidade|heterocigose]] para o xene XRCC1 mutado que codifica unha proteína XRCC1 truncada, suprime o crecemento de tumores en ratos nas tres condicións experimentais para inducir tres tipos de cancro (cancro de colon, melanoma ou cancro de mama).<ref name=Pettan-Brewer>{{cite journal |vauthors=Pettan-Brewer C, Morton J, Cullen S, Enns L, Kehrli KR, Sidorova J, Goh J, Coil R, Ladiges WC |title=Tumor growth is suppressed in mice expressing a truncated XRCC1 protein |journal=Am J Cancer Res |volume=2 |issue=2 |pages=168–77 |year=2012 |pmid=22432057 |pmc=3304571 |doi= |url=}}</ref>
MMEJ always involves at least a small deletion, so that it is a mutagenic pathway.<ref name=Liang>{{cite journal |vauthors=Liang L, Deng L, Chen Y, Li GC, Shao C, Tischfield JA |title=Modulation of DNA end joining by nuclear proteins |journal=J. Biol. Chem. |volume=280 |issue=36 |pages=31442–9 |year=2005 |pmid=16012167 |doi=10.1074/jbc.M503776200 |url=}}</ref> Several other pathways can also repair double-strand breaks in DNA, including the less inaccurate pathway of [[non-homologous end joining]] (NHEJ) and accurate pathways using [[homologous recombination]]al repair (HRR).<ref name="pmid24503142">{{cite journal |vauthors=Ottaviani D, LeCain M, Sheer D |title=The role of microhomology in genomic structural variation |journal=Trends Genet. |volume=30 |issue=3 |pages=85–94 |year=2014 |pmid=24503142 |doi=10.1016/j.tig.2014.01.001 |url=}}</ref> Various factors determine which pathway will be used for repair of double strand breaks in DNA.<ref name=Liang /> When FEN1, Ligase III, MRE11, NBS1, PARP1 or XRCC1 are over-expressed (this occurs with FEN1 when its promoter is hypomethylated<ref name=Singh />) the highly inaccurate MMEJ pathway may be favored, causing a higher rate of mutation and increased risk of cancer. ▼
▲MMEJ alwayssempre involvesimplica atpolo leastmenos aunha smallpequena deletiondeleción, sopolo thatque ité is aunha mutagenicvía pathwaymutaxénica.<ref name=Liang>{{cite journal |vauthors=Liang L, Deng L, Chen Y, Li GC, Shao C, Tischfield JA |title=Modulation of DNA end joining by nuclear proteins |journal=J. Biol. Chem. |volume=280 |issue=36 |pages=31442–9 |year=2005 |pmid=16012167 |doi=10.1074/jbc.M503776200 |url=}}</ref> Outras Severalvías otherpoden pathwaystamén canreparar alsoas repairroturas double-strandde breaksdobre infebra DNAdo ADN, includingincluíndo thea lessvía inaccuratemenos pathwayinexacta ofda [[ non-homologousunión endde joiningextremos non homólogos]] (NHEJ) ande accuratevías pathwaysmáis usingprecisas que usan a reparación por [[ homologousrecombinación recombinationhomóloga]] al repair (HRR).<ref name="pmid24503142">{{cite journal |vauthors=Ottaviani D, LeCain M, Sheer D |title=The role of microhomology in genomic structural variation |journal=Trends Genet. |volume=30 |issue=3 |pages=85–94 |year=2014 |pmid=24503142 |doi=10.1016/j.tig.2014.01.001 |url=}}</ref> Varios Variousfactores factorsdeterminan determinea whichvía pathwayque willse beusará usedpara forreparar repairas ofroturas doublede stranddobre breaksfebra inno DNAADN.<ref name=Liang /> WhenCando FEN1, a Ligase III, MRE11, NBS1, PARP1 orou XRCC1 areestán over-expressedsobreexpresados ( thisisto occursocorre withcon FEN1 whencando itso promoterseu is[[promotor]] é hypomethylatedhipometilado<ref name=Singh />) thea highlyvía inaccurateinexactra da MMEJ pathwaypode mayser be favoredfavorecida, causingcausando aunha highertaxa ratemaior ofde mutationmutación ande increasedun riskincremento ofdo risco de cancercancro.
Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is less usual in cancer. For instance, at least 36 DNA repair enzymes, when mutationally defective in germ line cells, cause increased risk of cancer (hereditary [[cancer syndrome]]s).<ref name=Bernstein>Bernstein C, Prasad AR, Nfonsam V, Bernstein H. (2013). DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-1114-6, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer</ref> (Also see [[DNA repair-deficiency disorder]].) Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers.<ref name=Bernstein /> (See also [[DNA repair#Frequencies of epimutations in DNA repair genes|Epigenetically reduced DNA repair and cancer]].) Ordinarily, deficient expression of a DNA repair enzyme results in increased un-repaired DNA damages which, through replication errors ([[DNA repair#Translesion synthesis|translesion synthesis]]), lead to mutations and cancer. However, FEN1, Ligase III, MRE1, PARP1, NBS1 and XRCC1 mediated MMEJ repair is highly inaccurate, so in these cases, over-expression, rather than under-expression, leads to cancer. This is supported by the observation that reduction of mutagenic XRCC1 mediated MMEJ repair leads to reduced progression of cancer.<ref name=Pettan-Brewer />
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Os cancros son moi a miúdo deficientes na expresión dun ou máis [[xene]]s de [[reparación do ADN]], pero a sobreexpresión dun xene de reparación do ADN é menos usual no cancro. Por exemplo, polo menos 36 [[encima]]s de reparación do ADN, cando son mutacionalmente defectuosos en células da liña xerminal, causan un incremento do risco de cancro (síndromes cancerosas hereditarias).<ref name=Bernstein>Bernstein C, Prasad AR, Nfonsam V, Bernstein H. (2013). DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-1114-6, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer</ref> De xeito similar, frecuentemente polo menos 12 xenes de reparación do ADN se atopan reprimidos [[epixenética|epixeneticamente]] nalgún ou en varios cancros.<ref name=Bernstein /> Ordinariamente, a expresión deficiente dun encima de reparación do ADN causa un incremento de danos no ADN non reparados, os cales, debido aos erros de replication ([[Reparación do ADN#Síntese translesión|síntese translesión]]), orixina mutacións e cancro. Porén, a reparación MMEJ mediada por FEN1, a Ligase III, MRE1, PARP1, NBS1 e XRCC1 é moi inexacta, de modo que neses casos, é a sobreexpresión envez da subexpresión a que conduce ao cancro. Isto está apoiado pola observación de que a redución da reparación MMEJ mediada por XRCC1 mutaxénico leva a unha redución da progresión do cancro.<ref name=Pettan-Brewer />
== Notas ==
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