Visão geral do reparo de DNA

DNA undergoes several thousand to a million damaging events daily from natural causes and external factors. Heat, radiation, oxidation by free radicals from cellular respiration, and hydrolytic reactions with water cause base chemistry alterations. Damage types include single-base alterations, base dimerization, chain breaks, and cross-linkage. These changes can lead to mutations if not repaired before cell division.

Deamination is a hydrolytic reaction where water causes loss of an amino group from pyrimidine bases like cytosine, converting it to uracil. This spontaneous damage occurs under physiological conditions and alters the base's chemical structure. If unrepaired, deamination leads to incorrect base-pairing during replication, causing mutations that can harm the genome or trigger cell death.

DNA's double-stranded structure contains two separate copies of genetic information in complementary strands. When one strand is damaged, the undamaged complementary strand serves as a template to restore the correct nucleotide sequence. This redundancy makes DNA particularly suitable for efficient repair, allowing cells to accurately fix most damage before replication occurs.

Base excision repair focuses on fixing endogenous DNA damage, particularly hydrolytic damage from deamination or depurination. This mechanism detects chemically modified bases, removes the damaged base or region, and synthesizes new DNA to restore the correct sequence. Base excision repair is one of three common mechanisms protecting cells from mutations and genome instability.

Nucleotide excision repair specifically targets damage caused by ultraviolet light and certain chemical carcinogens, unlike base excision repair which addresses hydrolytic damage. This mechanism detects the chemically modified DNA region, removes the damaged segment, and synthesizes replacement DNA. Nucleotide excision repair is essential for protecting cells from UV-induced mutations and carcinogenic damage.

If damage is beyond repair, cells undergo senescence or apoptosis. Senescence renders cells irreversibly dormant, halting the cell cycle indefinitely. Apoptosis triggers programmed cell death where caspases degrade cellular components, DNases digest DNA, and the cell shrinks. Macrophages then engulf and remove the cellular debris, preventing transmission of mutations to daughter cells.

Mismatch repair fixes faulty base incorporation by DNA polymerase during replication, correcting incorrect base-pairing errors. This mechanism detects mismatched bases, removes the incorrect nucleotide, and synthesizes the correct replacement. By correcting replication errors before cell division, mismatch repair prevents mutations from being transferred to daughter cells and maintains genomic stability.