DNA repair - global genome Nucleotide excision repair v 3.0 - Full HD

Nucleotide excision repair (NER), is a cellular DNA damage response induced by carcinogens such as: polycyclic aromatic hydrocarbons presents in tobacco (Benzo [α] pyrene), some cancer chemotherapy drugs (platinum-based treatments) or physical agents such as UV light. To activate this DNA repair mechanism, the lesions produced by the carcinogens (also called DNA-adduct) must distort the regular 3D structure of the DNA. Based on the chromatin estructure to be repaired, two NER sub-pathways can be identified. When the RNA polymerase II is stalled during transcription, due to the interception with an DNA lesion, the transcriptional-coupled NER (TC-NER) is activated to repair the transcriptionally active DNA strand. The rest of the genome is repaired by the global-genome NER (GG-NER).
Severe and rare diseases such as Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are characterized by autosomal and recessive mutations in NER genes. Both diseases are characterized by sunlight hypersensibility. An interesting observation comes from the fact that XP patients, has aproximately 1500 times higher risk to develope skin cancer than normal population, while CS patients are not at increased risk.
In molecular epidemiology population studies has been shown an increased risk of tobacco-related cancers including: lung, head and neck and bladder, with NER repair deficiency. On other hand, people with low NER efficiency, seems to be at increased risk to develope skin cancer, when a given number of sunburns are achieved.

But, How does NER repairs damaged-DNA?????

1) Three protein complexes are involved in DNA-damage recognition in NER pathway: XPA, XPC-HR23 and RPA.

2) These proteins recruits the Transcription factor II (TFIIH) that incorporate two helicases: XPB and XPD that unwinds a 30 bp DNA fragment around the DNA damage.

3) After DNA unwinding, damaged-DNA strand is excised by XPG and the XPF-ERCC1 complex at 3' and 5' sites respectively.

4) After excision, damaged-DNA strand is removed and replaced by re-synthesizing the template complementary DNA strand by polymerase complex (Pol. E/D, replication protein A (RPA) and replication factor C).

Category:

Science & Technology

Tags:

• carcinogenesis
• Xeroderma
• pigmentosum
• cockayne
• syndrome
• lung
• cancer
• tobacco
• smoke
• DNA
• repair
• defficiency
• skin
• ERCC1
• XPA
• XPD
• XPB
• RPA
• XPG
• TFIIH
• XPC
• HR23B
• cisplatin
• resistance
• increased
• risk
• of

[darkbluemars]

wow i understand it nowww.....

[RespectMyHate]

the theory of evolution is full of shit.

[biocjtr]

Great animation and a rather accurate depiction of NER, including the release of XPC prior to the dual incision step

[SuperElectricJohnson]

Some narration would go a long way though. Just to help people to place the different steps in their mind. Once again..nice video!

[SuperElectricJohnson]

Nice animation!

[retlifwolley]

This is great -- Thanks for posting