Nucleotide Excision Repair in Eukaryotes
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- Опубліковано 10 вер 2024
- Nucleotide excision repair in Prokaryotes :
• Nucleotide Excision Re...
Nucleotide excision repair is a DNA repair mechanism.DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR). While the BER pathway can recognize specific non-bulky lesions in DNA, it can correct only damaged bases that are removed by specific glycosylases. Similarly, the MMR pathway only targets mismatched Watson-Crick base pairs.
Nucleotide excision repair (NER) is a particularly important excision mechanism that removes DNA damage induced by ultraviolet light (UV). UV DNA damage results in bulky DNA adducts - these adducts are mostly thymine dimers and 6,4-photoproducts. Recognition of the damage leads to removal of a short single-stranded DNA segment that contains the lesion. The undamaged single-stranded DNA remains and DNA polymerase uses it as a template to synthesize a short complementary sequence. Final ligation to complete NER and form a double stranded DNA is carried out by DNA ligase. NER can be divided into two subpathways: global genomic NER (GG-NER or GGR) and transcription coupled NER (TC-NER or TCR). The two subpathways differ in how they recognize DNA damage but they share the same process for lesion incision, repair, and ligation.
The importance of NER is evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins. Xeroderma pigmentosum and Cockayne's syndrome are two examples of NER associated diseases.
Nucleotide excision repair is more complex in eukaryotes than prokaryotes, but the general principle is similar. There are 9 major proteins involved in NER in mammalian cells. Deficiencies in certain proteins leads to disease; protein names are associated with the disease. XPA, XPB, XPC, XPD, XPE, XPF, and XPG all derive from хeroderma pigmentosum and CSA and CSB represent proteins linked to Cockayne syndrome. Additionally, the proteins ERCC1, RPA, RAD23A, RAD23B, and others also participate in nucleotide excision repair.
Global genomic NER repairs damage in both transcribed and untranscribed DNA strands in active and inactive genes throughout the genome. This process is not dependent on transcription. This pathway employs several "damage sensing" proteins including the DNA-damage binding (DDB) and XPC-Rad23B complexes that constantly scan the genome and recognize helix distortions: the XPC-Rad23B complex is responsible for distortion recognition, while DDB1 and DDB2 (XPE) can also recognize some types of damage caused by UV light.
TC-NER initiates when RNA polymerase stalls at a lesion in DNA, whereupon protein complexes help move the polymerase backwards. Mutations in TC-NER machinery are responsible for multiple genetic disorders including:
Trichothiodystrophy (TTD): some individuals are photosensitive, ichthyosis, mental/physical retardation
Cockayne syndrome (CS): photosensitivity, mental retardation, progeria-like features, microcephaly
You have cleared all my confusion regarding this topic thank you sir. Very well explained
thanks for appreciation...Glad it helps...
Hi Shabir, Solid work!!! Tons of proteins with a few Zn++ or Mg++ loaded inside.Your videos always make me think about evolution--which is a very frustrating experience. The first 500M yrs earth cooled. The 2nd 500M yrs archaea formed. The next 1½B yrs eukaryotes formed. So I guess your video took about 2B yrs to happen.
7 subunits. That's easily 2 billion years.
Yes Dr. Mike... The evolution is damn amazing......and these little molecules are the building blocks to variations....
best explanation , thank you sir for clearning my doubt
You are most welcome
just stunned by the way u explain so complicated n complex topics in such an easy way. U are the mentor for many CSIR aspirants! looking forward to more such amazing videos packed with knowledge. Thank you Sir, your hardwork is worth appreciable.
thanks Kanica for appreciation..Glad u like my stuff ❤️❤️
thank you!!!
Sir ,You are far better than an IIT professor. Can you tell me where are you teaching right now?
I forgot to mention the scissors ✂️. I love the sound effect 🥰!
this was the last thing i added during editing ❤️
Sir your way of explanation is awesome... I like all your veils
Pleasw make vedio on Transposans
Very soon
bro you are like stunning amazing understanding clarity i enjoyed it
😍 love you
you should expand the content
Sir please make a video on mismatch repair mechanism