{"id":100563,"date":"2018-03-11T10:22:07","date_gmt":"2018-03-11T10:22:07","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/implicacion-de-la-dna-polimerasa-lambda-en-reparacion-de-dna-y-tumorogenesis\/"},"modified":"2018-03-11T10:22:07","modified_gmt":"2018-03-11T10:22:07","slug":"implicacion-de-la-dna-polimerasa-lambda-en-reparacion-de-dna-y-tumorogenesis","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-molecular\/implicacion-de-la-dna-polimerasa-lambda-en-reparacion-de-dna-y-tumorogenesis\/","title":{"rendered":"Implicaci\u00f3n de la dna polimerasa lambda en reparaci\u00f3n de dna y tumorog\u00e9nesis"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Gloria Mar\u00eda Terrados Aguado <\/strong><\/h2>\n<p>This doctoral thesis reports the purification of leishmania infantum dna polymerase beta (lipol\u00edY), as well as its characterization as a dna repair enzyme, with a metal preference for mn2+ over mg2+. Lipol\u00edY prefers gapped-dna substrates having a 5\u00c2\u00bf-p end, in agreement with its role in dna repair reactions. Purified lipol\u00edY also displayed a 5\u00c2\u00bf-deoxyribose-5-phosphate (drp) lyase activity, consistent with a \u00edYelimination mechanism. The concerted action of drp lyase and dna polymerization activities of lipol\u00edY on a uracil-containing dna suggests its participation in \u00c2\u00bfsinglenucleotide\u00c2\u00bf base excision repair (ber). Analysis of lipol\u00edY dna polymerization activity at different stages of the l. Infantum infective cycle supports a role for lipol\u00edY in parasite dna repair, counteracting the oxidative damage occurring inside the macrophage. dna polymerase lambda (pol\u00c2\u00bf), a recently described family x dna polymerase, has been also studied in this work regarding its in vivo role in dna repair and tolerance of oxidative damage. Analysis of the ber activity in tissue extracts from \u00c2\u00bfknock-out\u00c2\u00bf lambda mice (ko\u00c2\u00bf) indicated that pol\u00c2\u00bf is not essential for the ber of 8oxog:dc pairs. However, pol\u00c2\u00bf has a role in the correction of 8oxog:da to 8oxog:dc, thus minimizing 8oxog associated mutagenesis. Moreover, pol\u00c2\u00bf does not contribute to ber of either du:dg or 5fu:dg pairs in adult testis. However, our analysis suggests its participation in the ber of 5fu:dg in brain. In agreement with the participation of family x in translesion dna synthesis (tls) of 8oxog and 6mg and the possible role in ber of 5fu, we demostrated that hpol\u00edY, hpol\u00c2\u00bf and hpol\u00c2\u00bf are able to tolerate 5fu in dna, mainly inserting da in front of the lesion. Likewise, these three enzymes proficiently extended the pair 5fu:da, comparable to normal pairs dt:da y du:da, whereas they were very inefficient to extend the pair 5fu:dg. Moreover, they incorporated 5fdutp opposite da much better than opposite dg in the template. we have carried out the identification of two hpol\u00c2\u00bf splicing variants, that are highly expressed in different tumors. Hpol\u00c2\u00bf\u00c2\u00bf6 purification and enzymatic characterization suggests that the omision of exon 6 results in a poorly active variant, that could act as a dominant negative by sequestering nhej factors via interaction with its intact brct domain. we have identified and characterized a single nucleotide polymorphism (snp), of hpol\u00c2\u00bf, having a c\/t variation in the first base of codon 438, resulting in the amino acid change arg to trp. In vitro enzyme activity assays of the purified w438 pol\u00c2\u00bf variant revealed that it retained both dna polymerization and drp lyase activities, but had reduced base substitution fidelity. In agreement with this in vitro mutator phenotype, ectopic expression of the w438 hpol\u00c2\u00bfvariant in mammalian cells increased mutation frequency, affecting the dsb repair nhej pathway, and generating chromosome aberrations. All these phenotypes were dependent upon the catalytic activity of the w438 hpol\u00c2\u00bf. Rflp analysis in normal versus cancer patients demonstrated an association of the w438 polymorphism and rectal cancer.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Implicaci\u00f3n de la dna polimerasa lambda en reparaci\u00f3n de dna y tumorog\u00e9nesis<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Implicaci\u00f3n de la dna polimerasa lambda en reparaci\u00f3n de dna y tumorog\u00e9nesis <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Gloria Mar\u00eda Terrados Aguado <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 28\/04\/2010<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Luis Blanco D\u00e1vila<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: jose Fernandez piqueras <\/li>\n<li>enrique Viguera m\u00ednguez (vocal)<\/li>\n<li>Ana m. Alonso ayala (vocal)<\/li>\n<li>Jos\u00e9 Francisco Ruiz p\u00e9rez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Gloria Mar\u00eda Terrados Aguado This doctoral thesis reports the purification of leishmania infantum dna polymerase beta (lipol\u00edY), [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[36483],"tags":[179332,64806,204760,14602,84058,2617],"class_list":["post-100563","post","type-post","status-publish","format-standard","hentry","category-biologia-molecular","tag-ana-m-alonso-ayala","tag-enrique-viguera-minguez","tag-gloria-maria-terrados-aguado","tag-jose-fernandez-piqueras","tag-jose-francisco-ruiz-perez","tag-luis-blanco-davila"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/100563","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=100563"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/100563\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=100563"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=100563"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=100563"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}