DNA Damage and DNA Repair

DNA damage repair is a phenomenon that occurs when DNA molecules in biological cells recover their structure after being damaged by the action of various enzymes. The study of DNA damage repair helps to understand the mechanism of gene mutation, the causes of aging and cancer, and can also be applied to the detection of environmental carcinogens.

Fig 1. Types of DNA damage and DNA repair systems. (Moon et al., 2023)

What are DNA Damage and DNA Repair?

Types of DNA Damage

• Single-strand Breaks
  A break in one strand of a DNA double strand is called a single-strand break.
• Double-strand breaks
  A DNA double-strand break in the same or close proximity is called a double-strand break.
• DNA Cross-linking
  A covalent interaction between two strands of a DNA molecule or between side chains of different segments of the same DNA strand.
• Sugar Damage
  Sugar damage is a condition in which the sugar moiety of a DNA molecule is damaged or modified. This damage may include basic sites, oxidation of the sugar moiety, and other chemical modifications of the sugar moiety.
• Clustered Damage Sites
  Clustered DNA damage is characteristic of ionizing radiation and is defined as the formation of two or more damage sites within 20 bps of the passage of a single radiation track. Clustered DNA damage falls into two broad categories: double-strand breaks (DSBs) and non-DSB clusters, also known as oxidatively induced clustered DNA damage (OCDL), which may involve two opposing strands or the same strand.

Consequences of DNA Damage

a. Lethality.

b. Loss of certain functions.

c. Alteration of genotype without alteration of phenotype.

d. Occurs as a result that favors the survival of the species and allows organisms to evolve.

Types of DNA Repair

• Direct Repair - A method of repairing a damaged site directly by continuously scanning the DNA and identifying proteins at the site of the damage.
• Excision Repair (repairs most DNA damage) - Repairs a wide range of DNA damage including base shedding to form base-less sites, pyrimidine dimers, base alkylation, and single-strand breaks.
• Mismatch repair - Mismatch repair is a mechanism of biological DNA repair that mends mispaired bases in DNA. The process recognizes the correct strand, excises the incorrect portion, and then synthesizes correctly paired double-stranded DNA through the action of DNA polymerase III and DNA ligase.
• Double-strand Break Repair - Double-strand break repair is one of the most severe DNA damages to repair and involves the simultaneous breaking of both DNA strands. The main repair mechanisms include Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR).
• Recombination Repair (Post-Replication Repair) - The correct DNA is added to the faulty DNA sequence after replication.

DNA Repair Enzymes

Common DNA repair enzymes include ligases, endonucleases, exonucleases, polymerases, glycosylases, and methylases.

How do DNA Repair Mechanisms Work Synergistically?

• Regulation of Repair Prioritization
  Cells can regulate the activity and order of initiation of repair mechanisms to ensure that the most severe or high-risk DNA damage is prioritized for repair.
• Cross-Support of Repair Mechanisms
  Some repair mechanisms may cross-support each other in repairing specific types of DNA damage.
• Signaling and Regulation of Repair Mechanisms
  Cellular signaling pathways sense the presence of DNA damage and regulate the initiation, activity, and prioritization of repair mechanisms.

Reference

1. Moon J, et al. DNA Damage and Its Role in Cancer Therapeutics[J]. International Journal of Molecular Sciences, 2023, 24(5): 4741.