Discusses the ways radiation damage can lead to mutations or genomic instability, and how cells respond and repair damages.
Introduction to radiation: Radiation is the transfer of energy from one object to another. There are different types of radiation, including ionizing and non-ionizing radiation. Ionizing radiation is high-energy radiation that can cause DNA damage.
DNA structure and function: DNA is a double-stranded helix that carries genetic information. The DNA structure is important for understanding how radiation-induced damage occurs and how it is repaired.
Types of DNA damage: There are different types of DNA damage, including base damage, single-strand breaks, and double-strand breaks. Radiation can cause all of these types of damage.
Molecular mechanisms of DNA damage and repair: There are different molecular mechanisms involved in DNA damage and repair, including base excision repair, nucleotide excision repair, and double-strand break repair.
Radiation effects on cellular processes: Radiation can affect various cellular processes, including DNA replication, transcription, and translation.
Dose-response relationships: The relationship between radiation dose and biological response is nonlinear and influenced by various factors, including dose rate, radiation quality, and genetic factors.
Radiation-induced cancers: Radiation-induced cancers occur when radiation damages DNA in cells that control cell division. Ionizing radiation is a known carcinogen.
Radiation protection and safety: Radiation safety is important in both medical and occupational settings. Radiation protection measures include shielding, time, and distance.
Medical applications of radiation: Radiation is used in medicine for diagnostic and therapeutic purposes. Radiation oncology is a field that uses radiation to treat cancer.
Future directions in radiation biology: Research is ongoing in radiation biology to understand the long-term effects of radiation exposure and to develop new strategies to prevent and treat radiation-induced DNA damage.
Single-strand breaks: This is when the DNA strand is broken but the other strand remains intact. This type of damage is usually repaired quickly by the base excision repair pathway.
Double-strand breaks: This type of damage is caused when both strands of DNA are broken. It is a severe form of DNA damage, and it can lead to cell death or cancerous transformation. The two primary repair mechanisms for double-strand breaks are homologous recombination and non-homologous end joining.
Oxidative damage: This occurs when oxygen radicals react with DNA and cause chemical alterations to the DNA structure. The repair pathway for oxidative damage is called the base excision repair pathway.
Cross-links: This is when two strands of DNA are chemically linked together, and it causes DNA to become tangled. This type of damage is repaired by nucleotide excision repair.
Base damage: When a nucleotide base is altered or removed, it can cause damage to DNA. The repair mechanism for base damage is also the base excision repair pathway.
Tandem lesions: This is when there is more than one lesion (damage) in close proximity. The repair mechanisms for tandem lesions can be complicated and involve multiple pathways.
DNA-protein cross-links: This type of damage occurs when proteins bind to DNA and prevent replication and transcription. The repair of DNA-protein cross-links involves nucleotide excision repair and proteolysis.
Cluster damage: This is when multiple DNA damages are formed within a short distance. This damage is repaired by inter-play between base excision repair, nucleotide excision repair, and homologous recombination.
Radiation-induced mutations: Radiotherapy also causes mutations in the DNA, seen by the expression of its genes.
Abasic sites: Also called apurinic/apyrimidinic, AP sites are where a base on one or the other strand of DNA has been lost. AP sites occur in DNA due to spontaneous hydrolysis, depurination, or due to DNA damage from a mutagenic agent like radiation itself. This type of DNA damage is repaired by base-excision repair or nucleotide-excision repair.
Mismatched nucleotides: Mismatched nucleotides or mismatches occur when a wrong nucleotide, which is not a base-pair match to its partner, is inserted during DNA replication. This can be repaired using mismatch repair, which removes the mismatch by recoding the incorrect base that has paired with an opposite allele.
Strand-invasion defects: Radiation can also induce large-scale rearrangements of the genome, making it difficult to locate damage. The DNA double-strand break (DSB) can be repaired via non-homologous end-joining (NHEJ), which requires a variety of proteins, including several nucleases to process the ends of the DSB, promoting correct end joining of the broken strands.
DNA-damage checkpoints: Irradiation causes damage to the DNA and induces DNA-damage checkpoints, which stop the progression of replication until damaged DNA is repaired.
Proteomic studies have provided new ideas in radiation-induced DNA damage include the roles of enzymes, phosphoproteins, chromatin remodeling enzymes, and nuclear matrix proteins.: Proteomic studies shed light on the involvement of various proteins, such as enzymes, phosphoproteins, chromatin remodeling enzymes, and nuclear matrix proteins, in radiation-induced DNA damage and repair mechanisms.