Wednesday, May 21, 2014

Neucleotide Excision Repair !!! ... (2/4)

Neucleotide Excision Repair (NER) is a particularly important excision mechanism which removes DNA damage induced by ultraviolet (UV) light. UV DNA damage results in bulky DNA adducts (a DNA adduct is a piece of DNA covalently bonded to cancer-causing chemical. This process could be the start of a cancerous cell or carcinogenesis) ¾ mostly pyrimidine/thymine dimmers, 6, 4- photoproducts.

Recognition of the damage leads to removal of a short single stranded DNA segment which contains the lesions. The undamaged single stranded DNA remains and DNA polymerase use 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 2 sub-pathways ¾

E Global Genomic NER (GG-NER)
E Transcription Coupled NER (TC-NER)

The two sub-pathways differ in how they recognize DNA damage but they share the same process for lesions incision, repair and ligation.

In TCR, stalled RNA Polymerase, at DNA damage position, is the signal to initiate NER whereas in GGR, the signal is the helix distortion by the damage.

The assembly of the NER complex starts with DNA damage recognition, followed by binding of addition factors including the basal transcription factor ‘TFIIH’. This factor contains the XPB & XPD genes.

The incision step is carried out by two endonuclease ¾ XPF-ERRC1 and XPG ¾ leading to excision of DNA lesion.

XP indicate the 7 NER genes mutated in XP patient.

Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity

Source: Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity

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