DNA Damage and Repair Mechanisms

A type of DNA damage that arises from internal cellular processes.

Errors in DNA replication that occur when incorrect nucleotides are inserted during DNA copying.

Enzymes involved in removing supercoiling in DNA, but can also cause damage if DNA ends misalign.

Reactive oxygen species (ROS) that can cause oxidative damage to DNA, leading to lesions and modifications.

A DNA repair mechanism that directly fixes specific types of DNA damage without excision or replacement.

Base excision repair (BER) is a DNA repair pathway that removes damaged or modified bases from DNA. It involves several steps:

1. Recognition and Removal: A DNA glycosylase identifies the damaged base and removes it from the DNA backbone.
2. AP Site Cleavage: An AP endonuclease cleaves the phosphodiester backbone near the AP site (apurinic/apyrimidinic site), where the base is missing.
3. Gap Filling: DNA polymerase I fills the gap created by the AP endonuclease, using the undamaged strand as a template. It also removes the damaged section from the strand.
4. Nick Sealing: DNA ligase seals the remaining nick, completing the repair.

Nucleotide excision repair (NER) is a DNA repair pathway that removes bulky DNA lesions, such as those caused by UV radiation or chemicals. It includes the following steps:

1. Recognition and Excision: A complex of proteins recognizes the bulky lesion and cleaves the damaged DNA strand on either side of the lesion.
2. Segment Removal: A helicase unwinds the DNA, and the damaged segment (usually 13 or 29 nucleotides) is removed.
3. Gap Filling: DNA polymerase fills the gap with the correct sequence, using the undamaged strand as a template.
4. Nick Sealing: DNA ligase seals the remaining nick, completing the repair.

Mismatch repair (MMR) is a DNA repair pathway that corrects mismatched base pairs that can occur during DNA replication. MMR is crucial for maintaining genetic stability and preventing mutations. Here's how it works:

1. Mismatched Recognition: Protein complexes like MutS recognize the mismatch errors in the DNA.
2. Excision and Degradation: Exonuclease 1 (Exo1) degrades the error-containing strand. Replication protein A (RPA) stabilizes the exposed DNA.
3. Resynthesis: DNA polymerase synthesizes the correct sequence, using the undamaged strand as a template.
4. Nick Sealing: DNA ligase seals any remaining nicks, completing the repair.

Lynch Syndrome is a hereditary condition caused by mutations in MMR genes. It increases the risk of developing various cancers, including colon, ovarian, and other types of cancer. People with Lynch Syndrome are at increased risk because their MMR system isn't functioning properly, allowing errors in DNA replication to accumulate and eventually lead to cancer development.

MutS and MutL are crucial protein complexes involved in the mismatch repair (MMR) pathway. MutS recognizes mismatched base pairs, whileMutL helps recruit other repair proteins to the site of the mismatch. In E. coli, MutH is also important for MMR. Together, these proteins ensure that DNA replication errors are corrected efficiently.