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DNA repair is a collection of processes (Biological pathway) by which a cell identifies and corrects damage to the DNA molecules that encode its genome. (http://en.wikipedia.org/wiki/DNA_repair)

관련 유전자들은 이 페이지 참고 DNA repair-deficiency disorder

DNA damage and mutation #

Source of damage

  1. Endogenous
    1. Reactive oxygen species
    2. Replication errors
  2. Exogeneous
    1. UV radiation
    2. x-ray and gamma rays
    3. hydrolysis or thermal disruption
    4. certain plant toxins
    5. human-made mutagenic chemicals, expecially compounds that act as DNA intercalating agents
    6. viruses

Types of damage

  1. oxidation of bases
  2. alkylation of bases (methylation)
  3. hydrolysis of bases (deamination, depurination, depyrimidination)
  4. mismatche of bases
  5. monoadduct damage cause by change in single nitrigenous base of DNA
  6. disadduct damage

DNA repair mechanisms #

Direct reversal #

  1. photoreactivation process directly reversed by phtolyase (not human)
  2. methylation of G directly reversed by guanine methyl transferase (MGMT)
  3. methylation of C and A

Single-strand damage #

  1. Base excision repair (BER): single nitrogeneous base by glycosylase
  2. Nucleotide excision repair (NER): pyrimidine dimerization cased by UV
  3. DNA mismatch repair

Double-strand breaks (DSBs) #

It can make genome rearrangement

  1. Non-homologous end joining (NHEJ): DNA Ligase IV, XRCC4 directly joins two ends -- can lead to deletion, insertion, translocation
  2. Microhomology-mediated end joining (MMEJ): MRE11, PARP1 is required.
  3. Homologous recombination

Translesion synthesis #

Translesion synthesis (TLS) is a DNA damage tolerance process that allows the DNA replication machinery to replicate past DNA lesions such as thymine dimers or AP sites.

Global response to DNA damage #

DNA damage checkpoints

Genes #

관련정보 #


DNA repair 메커니즘은 나이를 먹으면서(Ageing), 그 정교함을 잃어버리도록 설계되어 있는지도 모른다. 그렇다면 노화와 변이에 관한 두가지 궁금한 것의 이유를 유추할 수 있다.

  1. 자손에게 전달되는 germline 변이는 상대적으로 적다. (생명 역사를 거쳐 살아있으려면 적어야 한다.)
  2. 종의 번영을 위해 노화는 미리 계획되어 있다.

이 둘을 만족시키는 답은 DNA repair의 고장이다. 자손을 나은 이후 즈음되는 나이부터는 관련 유전자들의 활성이 떨어지도록 설계되어 있는거지. 그럴듯한 상상.

--Hyungyong Kim, 2016-01-25

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