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