nukleotidiexkisionreparoinnilla

Nukleotidiexkisionreparoinnilla, also known as nucleotide excision repair (NER), is a crucial cellular mechanism that repairs damaged DNA. It is particularly effective at removing bulky, helix-distorting lesions such as those caused by UV radiation, chemical mutagens, and certain DNA adducts. NER operates through a multi-step process involving several protein complexes.

The pathway begins with damage recognition. In eukaryotes, two main sub-pathways exist: global genome NER (GG-NER) and transcription-coupled NER (TC-NER). GG-NER surveys the entire genome for damage, mediated by proteins like XPC and XPA. TC-NER, on the other hand, is triggered when RNA polymerase stalls at a lesion during transcription, recruiting repair factors like CSA and CSB.

Once damage is detected, a multi-subunit complex, including XPB and XPD helicases, unwinds the DNA around the lesion. This creates a bubble of single-stranded DNA. Then, endonucleases, such as XPG and XPF-ERCC4, make incisions on either side of the damaged nucleotides. Following the incisions, a segment of the damaged DNA, typically 12-30 nucleotides in length, is excised.

Finally, DNA polymerase synthesizes new DNA to fill the gap, using the undamaged strand as a template. DNA ligase then seals the nick in the phosphodiester backbone, completing the repair. Deficiencies in NER genes are associated with a number of human genetic disorders, most notably xeroderma pigmentosum, which is characterized by extreme sensitivity to sunlight and a significantly increased risk of skin cancer.