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=== Sobreexpresión de PARP1 no cancro ===
A PARP1 isé oneun ofdos sixseis enzymesencimas requirednecesarios forpara thea highlyvía error-pronede DNAreparación repairdo pathwayADn tendente ao erro da [[ microhomology-mediatedunión endde joiningextremos mediada por microhomoloxía]] (MMEJ).<ref name="pmid25789972">{{cite journal |vauthors=Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC |title=Homology and enzymatic requirements of microhomology-dependent alternative end joining |journal=Cell Death Dis |volume=6 |issue= |pages=e1697 |year=2015 |pmid=25789972 |doi=10.1038/cddis.2015.58 |url= |pmc=4385936}}</ref> A MMEJ isestá associatedsociada withcon frequentfrecuentes chromosomeanormalidades abnormalities suchcromosómicas, ascomo deletionsdelecións, translocationstranslocacións, inversionsinversións ande otheroutros complexcomlexos rearrangementsrearranxos cromosómicos. Cando Whena PARP1 isé up-regulatedregulada á alza, MMEJincreméntase isa increasedMMEJ, causingcausando [[ genomeinestabilidade instabilityxenómica]].<ref name=Muvarak>{{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 |pmc=4398615 |doi=10.1158/1541-7786.MCR-14-0422 |url=}}</ref> Nas PARP1leucemias iscon up-regulatedtirosina andquinase MMEJactivada isa increasedPARP1 iné tyrosineregulada kinase-activatedá alza e a MMEJ leukemiasincreméntase.<ref name=Muvarak /> ▼
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▲PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway [[microhomology-mediated end joining]] (MMEJ).<ref name="pmid25789972">{{cite journal |vauthors=Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC |title=Homology and enzymatic requirements of microhomology-dependent alternative end joining |journal=Cell Death Dis |volume=6 |issue= |pages=e1697 |year=2015 |pmid=25789972 |doi=10.1038/cddis.2015.58 |url= |pmc=4385936}}</ref> MMEJ is associated with frequent chromosome abnormalities such as deletions, translocations, inversions and other complex rearrangements. When PARP1 is up-regulated, MMEJ is increased, causing [[genome instability]].<ref name=Muvarak>{{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 |pmc=4398615 |doi=10.1158/1541-7786.MCR-14-0422 |url=}}</ref> PARP1 is up-regulated and MMEJ is increased in tyrosine kinase-activated leukemias.<ref name=Muvarak />
A PARP1 istamén alsose over-expressedsobreexpresa whencando itsa promotersúa regionrexión promotora do sitio [[ETS1|ETS]] siteé ishipometilada [[epigeneticsepixenética|epigeneticallyepixeneticamente]] hypomethylated, ande thisisto contributescontribúe toa progressionprogresión todo cancro endometrial cancer,<ref name="pmid23762867">{{cite journal |vauthors=Bi FF, Li D, Yang Q |title=Hypomethylation of ETS transcription factor binding sites and upregulation of PARP1 expression in endometrial cancer |journal=Biomed Res Int |volume=2013 |issue= |pages=946268 |year=2013 |pmid=23762867 |pmc=3666359 |doi=10.1155/2013/946268 |url=}}</ref> cancro de ovario con BRCA-mutated ovarian cancermutado,<ref name="pmid24448423">{{cite journal |vauthors=Li D, Bi FF, Cao JM, Cao C, Li CY, Liu B, Yang Q |title=Poly (ADP-ribose) polymerase 1 transcriptional regulation: a novel crosstalk between histone modification H3K9ac and ETS1 motif hypomethylation in BRCA1-mutated ovarian cancer |journal=Oncotarget |volume=5 |issue=1 |pages=291–7 |year=2014 |pmid=24448423 |pmc=3960209 |doi=10.18632/oncotarget.1549 |url=}}</ref> ande BRCA-mutatedcancro serousde ovarianovario cancerseroso con BRCA mutado.<ref name="pmid23442605">{{cite journal |vauthors=Bi FF, Li D, Yang Q |title=Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer |journal=BMC Cancer |volume=13 |issue= |pages=90 |year=2013 |pmid=23442605 |pmc=3599366 |doi=10.1186/1471-2407-13-90 |url=}}</ref>
A PARP1 istamén alsose over-expressedsobreexpresa innoutros acancros, number of other cancers,como includingo 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> testicular and other germ cell tumors,<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> Ewing’s sarcoma,<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|url=}}</ref> malignantlinfoma lymphomamaligno,<ref name="pmid1907096">{{cite journal |vauthors=Tomoda T, Kurashige T, Moriki T, Yamamoto H, Fujimoto S, Taniguchi T |title=Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma |journal=Am. J. Hematol. |volume=37 |issue=4 |pages=223–7 |year=1991 |pmid=1907096 |doi= 10.1002/ajh.2830370402|url=}}</ref> breastcancro cancerde mama,<ref name="pmid21908496">{{cite journal |vauthors=Rojo F, García-Parra J, Zazo S, Tusquets I, Ferrer-Lozano J, Menendez S, Eroles P, Chamizo C, Servitja S, Ramírez-Merino N, Lobo F, Bellosillo B, Corominas JM, Yelamos J, Serrano S, Lluch A, Rovira A, Albanell J |title=Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer |journal=Ann. Oncol. |volume=23 |issue=5 |pages=1156–64 |year=2012 |pmid=21908496 |doi=10.1093/annonc/mdr361 |url=}}</ref> and colon cancer.<ref name="pmid25526641">{{cite journal |vauthors=Dziaman T, Ludwiczak H, Ciesla JM, Banaszkiewicz Z, Winczura A, Chmielarczyk M, Wisniewska E, Marszalek A, Tudek B, Olinski R |title=PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1 |journal=PLoS ONE |volume=9 |issue=12 |pages=e115558 |year=2014 |pmid=25526641 |pmc=4272268 |doi=10.1371/journal.pone.0115558 |url=}}</ref>
Os cancros son moi a miúdo ''deficientes'' na expresión dun ou máis xenes de reparación do ADN, pero a ''sobreexpresión'' dun xene de reparación do ADN é menos usual no cancro. Por exemplo, polomenos 36 encimas de reparación do ADN, cando son mutacionalmente defectivos nas células da liña xerminal, causan un incremento do risco de padecer cancro ([[síndrome de cancro|síndromes de cancro]] hereditarios ou familiares).<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, atopáronse frecuentemente polo menos 12 xenes de reparación do ADN que son reprimidos epixeneticamente nun ou máis cancros.<ref name=Bernstein /> Normalmente, a expresión deficiente dun encima de reparación do ADN orixina un incremento dos danos no ADN non reparados, que por medio de erros de replicación (ver [[reparación do ADN#Síntese translesión|síntese translesión]]), causan mutacións e cancro. Porén, a reparación pola vía [[MMEJ]] mediada pola PARP1 é moi inexacta, polo que neste caso, é a sobreexpresión en vez da subexpresión a que aparentemente conduce ao cancro.
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, PARP1 mediated [[microhomology-mediated end joining|MMEJ]] repair is highly inaccurate, so in this case, over-expression, rather than under-expression, apparently leads to cancer.
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=== Interacción con BRCA1 e BRCA2 ===
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