5- Mutaciones y Reparaciones Del ADN

Lesiones y Reparación del ADN

Lesión (alteración química en el ADN)

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Mutación (Modificación en la secuencia del ADN)

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Mutación: Cambio en la secuencia nucleotídica de una región corta de un genoma. Se producen por errores de la replicación del ADN o por acción de mutágenos (agentes químicos y radiación). Deficiencia en la reparación del ADN. Tipos de mutaciones: Puntuales (transiciones y transv t ransversiones). ersiones). Inserciones Deleciones Efectos de las mutaciones: Letales o no letales. Organismos

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Categoría de mutaciones Espontánea vs inducida



Somática vs germinal



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Tipos de mutaciones Cambios a nivel de un nucleótido (puntuales) en el ADN:

Sustitución de bases

Inserciones y deleciones

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Tipos de mutaciones

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Alteraciones Alter aciones químicas producidas en las bases nitrogenadas

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Agentes alquilantes: metilmetano sulfonato (mutágeno químico), añade grupos alquilo a las bases nucleotídicas. El efecto depende de la posición en la que es modificado el

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Las radiaciones ionizantes Producen diversos efectos que dependen del tipo de radiación y de su intensidad. Pueden actuar de forma indirecta al estimular la formación de moléculas reactivas, como peróxidos en las células.  Acción de los radicales libres sobre el DNA DNA

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Desaminación del ADN: la eliminación del grupo amino ocurre espontáneamente a baja frecuencia, que puede ser aumentada por agentes químicos químicos (ácido nitroso: desamina A, C, G, T no tiene tiene grupo amino). Bisulfito de sodio: desamina C. La pérdida también puede ser espontanea dependiente de temperatura y pH. 

CG UA TA

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Mutaciones causadas por mutágenos químicos  Análogos de bases. Son bases púricas y pirimidínicas que presentan similitud a las bases convencionales y se incorporan erróneamente como 

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Efecto mutágeno del 5-bromouracilo

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Pérdida de bases

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Radiación UV:

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Reparación de errores de replicación Reparación de bases desapareadas (“ (“mismatch mismatch repair ”) ”)

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Los eucariotas tienen un sistema de reparación similar. El reconocimiento de la cadena recientemente sintetizada se realiza por la presencia de roturas en ambos extremos de los fragmentos de Okazaki, mientras que la hebra conductora se puede identificar por su extremo 3´en crecimiento. Cáncer colorectal hereditario no poliposo (HNPCC) o síndrome sínd rome de Lynch

Consecuencia de un defecto en los mecanismos de reparación de los apareamientos incorrectos

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Los pequeños lazos de ADN que se incorporan durante la replicación se pueden producir cuando…

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Sistemass de reparación inducibles Sistema Se activan cuando hay un daño extenso al DNA. En bacterias es el sistema SOS. Se activa con daño extenso ej. UV La tasa de mutación es más alta después de la reparación por este sistema que si no existiera. Mutantes sin sistema SOS presentan menor tasa de

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Reparación por síntesis de translesión  “trans lesion synthesis” (TLS) ¿Qué ocurre si la DNA pol de replicación encuentra una lesión, dímero de T o un sitio AP, que no ha sido

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Reparación Repar ación por síntesis de translesión (TLS) Polimerasas de translesión: Familia Y de DNA polimerasas

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Reparación de roturas de doble cadena Las roturas de doble cadena son potencialmente potencialmente letales Causas de rotura de doble hebra • Radiaciones ionizantes (rayos g, rayos X) • Especies de oxígeno reactivas

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Reparación Re paración mediante Unión de Extremos No Homólogos (propenso a error) •

Los extremos rotos son alineados y recortados, luego son ligados.

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Reparación Repar ación mediante recombinación con secuencias homólogas Las roturas de cadena simple pueden repararse utilizando la cadena de ADN intacta, utilizandola como dadora de información de secuencia. Las roturas de doble cadena, pueden repararse utilizando la información faltante de otro DNA de doble cadena, que puede provenir de:

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Reparación de Rotura de ADN Reparación de doble cadena mediante

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Reparación de roturas de doble cadena mediante recombinación homóloga