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Liña 14:
== A MMEJ no cancro ==
 
O xene da [[endonuclease]] [[FEN1]] está sobreexpresado na maioría dos cancros de mama,<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> de próstata,<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> estómago,<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> pancreático,<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> e de pulmón.<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>
 
A [[LIG3|Ligase III]] está regulada á alza na leucemia 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> mieloma múltiple,<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> e cancro de mama.<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>
 
O xene da proteína [[MRE11A|MRE11]] sobreesprésasedsobreesprésase en cancros de mama.<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>
 
A [[Nibrina|NBS1]] está sobreexpresadosobreexpresada nalgúns cancros de próstata,<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> en cancro de cabeza e pescozo,<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> ande inen squamouscarcinoma cellde carcinomacélulas ofescamosas theda oralcavidade cavityoral.<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 [[polimerase]] [[PARP1]] está sobreexpresadosobreexpresada nas leucemias activadas por [[tirosina quinase]],<ref name="pmid25828893">{{cite journal |vauthors=Muvarak N, Kelley S, Robert C, Baer MR, Perrotti D, Gambacorti-Passerini C, Civin C, Scheibner K, Rassool FV |title=c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in 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> en neuroblastoma,<ref name="pmid25563294">{{cite journal |vauthors=Newman EA, Lu F, Bashllari D, Wang L, Opipari AW, Castle VP |title=Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma |journal=Mol. Cancer Res. |volume=13 |issue=3 |pages=470–82 |year=2015 |pmid=25563294 |doi=10.1158/1541-7786.MCR-14-0337 |url=}}</ref> en tumors testiculares e de [[liña xerminal|células xerminais]],<ref name="pmid23486608">{{cite journal |vauthors=Mego M, Cierna Z, Svetlovska D, Macak D, Machalekova K, Miskovska V, Chovanec M, Usakova V, Obertova J, Babal P, Mardiak J |title=PARP expression in germ cell tumours |journal=J. Clin. Pathol. |volume=66 |issue=7 |pages=607–12 |year=2013 |pmid=23486608 |doi=10.1136/jclinpath-2012-201088 |url=}}</ref> e no sarcoma de Ewing.<ref name="pmid11956622">{{cite journal |vauthors=Newman RE, Soldatenkov VA, Dritschilo A, Notario V |title=Poly(ADP-ribose) polymerase turnover alterations do not contribute to PARP overexpression in Ewing's sarcoma cells |journal=Oncol. Rep. |volume=9 |issue=3 |pages=529–32 |year=2002 |pmid=11956622 |doi= 10.3892/or.9.3.529}}</ref>
 
O xene da proteína [[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|heterocigoseheterocigoto]] para o xene XRCC1 mutado que codifica unha proteína XRCC1 truncada, suprime o crecemento de tumores en ratos nasen 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>
 
A MMEJ sempre implica polo menos unha pequena deleción, polo que é unha vía mutaxénica.<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 vías poden tamén reparar as roturas de dobre febra do ADN, incluíndo a vía menos inexacta da [[unión de extremos non homólogos]] (NHEJ) e vías máis precisas que usan a reparación por [[recombinación homóloga]].<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 factores determinan a vía que se usará para reparar as roturas de dobre febra no ADN.<ref name=Liang /> Cando FEN1, a Ligase III, MRE11, NBS1, PARP1 ou XRCC1 están sobreexpresados (isto ocorre con FEN1 cando o seu [[promotor (xenética)|promotor]] é hipometilado<ref name=Singh />) a vía inexactrade baixa precisión da MMEJ pode ser favorecida, causando unha taxa maior de mutación e un incremento do risco de cancro.
 
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 />
Traído desde «https://gl.wikipedia.org/wiki/Unión_de_extremos_mediada_por_microhomoloxía»