RESUMO
The stability of cell genetic material is influenced by a variety of factors, both internal and external, which can cause various types of DNA damage, such as DNA alkylation, oxidation, mismatching, loop structure, atypical DNA structure, single-strand break, and double-strand break.These DNA damages disrupt cellular homeostasis and dynamic equilibrium, which cause gene mutations, chromosomal abnormalities, and even degradation, aging, and death at different biological levels.By searching and identifying DNA damage sites, the cell activates a series of biochemical pathways, coordinates the progress of DNA replication and transcription, and then repairs the DNA damage.In this way, the cell maintains its independence and stability.While radiotherapy plays a role in eliminating tumors by DNA damages, it also initiates DNA damage responses.Among the responses, base excision repair, nucleotide excision repair, mismatch repair, double-strand break repair, and post-translesion synthesis repair play a key role in repairing the damages.The dysfunction of these repair pathways will cause differences in tumor radiation sensitivity.This paper summarizes recent research results in DNA damage repair, and focuses on the types of DNA damage and their repair mechanisms, so as to promote the understanding of the great significance of this field and to provide a theoretical basis for exploring the application of DNA damage repair pathways in tumor therapy.
RESUMO
Las células cuentan con mecanismos complejos que vigilan la integridad del ADN, activando mecanismos de reparación cuando hay deficiencias o errores durante la replicación. Una consecuencia potencial de los daños son las alteraciones permanentes en la estructura del ADN que pueden generar mutaciones, transformación carcinogénica y muerte celular. Estos son atribuidos a diferentes agentes endógenos como los radicales libres de oxígeno (RLO) provenientes de la respiración, los cuales son considerados el centro de la carcinogénesis y el envejecimiento por daño genómico; agentes exógenos como la luz ultravioleta que inducen dímeros de pirimidina y la radiación ionizante que produce una gran variedad de daños sobre las bases, muchos de ellos por efecto indirecto. También se encuentran las genotoxinas presentes en los alimentos, humo de tabaco y agentes quimioterapéuticos, con grandes cualidades para alterar la estructura de la molécula ADN e interferir con su expresión. De esta manera, cerca de 10(5) lesiones espontáneas por día son inducidas en nuestros genes, en donde los mecanismos de reparación detectan daños y perturbaciones durante el crecimiento y división celular. Esto es posible gracias a las funciones específicas de reconocimiento, corrección o eliminación de daños que asegura la integridad del genoma. En este artículo se presentan los principales mecanismos de reparación del ADN, su relación y activación de acuerdo al tipo de daño.
Cells have complex mechanisms that monitor DNA integrity that activate repair mechanisms when there are deficiencies or errors during replication. A potential result of the damage is a permanent alteration in DNA structure that can generate mutations, carcinogenic transformation and cell death. These are attributed to different endogenous agents such as oxygen free radicals (OFR) from respiration, which are considered the center of carcinogenesis and aging process due to genomic damage; exogenous agents, such as ultraviolet light, induce pyrimidine dimers and ionizing radiation that produce a variety of damage on the bases, many by indirect effect. Genotoxins present in food, tobacco and chemotherapeutic agents are also found with high potential in altering the DNA molecule structure and interfering with its expression. Thus, around 10(5) spontaneous lesions are induced per day in our genes, where the repair mechanisms can detect damages and disturbances during cell growth and division. This is possible thanks to the specific recognition, correction or elimination of damage functions, ensuring the integrity of the genome. In this article the main mechanisms of DNA repair, as well as their relationship and activation according to the type of damage, are presented.