DNA repair

DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in as many as 1 million individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. Consequently, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinking, leading to mutations and possibly cancer.

Types of DNA Damage

DNA damage can be classified into two main types:

• Single-strand breaks (SSBs), which affect only one of the two DNA strands
• Double-strand breaks (DSBs), which affect both strands in the DNA double helix

Other forms of damage include base modifications such as oxidative damage, alkylation, or hydrolysis that lead to base loss or mismatch.

Mechanisms of DNA Repair

Several distinct mechanisms have evolved to repair DNA damage. These include:

• Direct reversal, which chemically reverses damage without breaking the DNA helix. An example is the repair of methylated bases.
• Base excision repair (BER), which corrects DNA containing a damaged DNA base.
• Nucleotide excision repair (NER), which removes bulky DNA damage and other types of helix-distorting damage.
• Mismatch repair (MMR), which corrects errors of DNA replication and recombination that result in mispaired (but undamaged) nucleotides.
• Homologous recombination repair (HRR), which repairs double-strand breaks or interstrand cross-links.
• Non-homologous end joining (NHEJ), which directly ligates the broken ends of DNA together.

DNA Repair and Cancer

Defects in the DNA repair process can lead to cancer. Cells with mutations in key DNA repair genes may experience an increase in the rate of spontaneous mutations, leading to a higher risk of cancer. For example, mutations in the BRCA1 and BRCA2 genes, which are involved in homologous recombination repair, are known to increase the risk of breast cancer and ovarian cancer.

DNA Repair and Aging

There is evidence to suggest that the accumulation of DNA damage over time is a major contributor to the aging process. As organisms age, the efficiency of DNA repair mechanisms decreases, leading to the accumulation of damage and the potential for cellular dysfunction.

See Also

• Genome stability
• Oxidative stress
• Senescence
• Somatic hypermutation