3 Xeroderma pigmentosum and related disorders: Defects in DNA repair and transcription

摘要: The genetic disorders xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD) are all associated with defects in nucleotide excision repair (NER) of DNA damage. Their clinical features very different, however, XP being a highly cancer-prone skin disorder, whereas CS TTD cancer-free multisystem disorders. All three genetically complex, at least eight complementation groups for (XP-A to -G variant), five (CS-A, CS-B, XP-B, XP-D, XP-G), (XP-B, TTD-A). With the exception variant, products genes proteins involved different steps NER, comprise damage-recognition proteins, two helicases, nucleases. XPB XPD, components basal transcription factor TFIIH, which has dual role NER initiation transcription. Different mutations these can affect differentially, this accounts phenotypes. Mutations resulting defective without affecting result XP, if is also affected, outcome. only transcription-coupled repair, subpathway damage transcribed strands active rapidly preferentially repaired. Current evidence suggests that they have an important but not essential variant form novel polymerase, able synthesise past UV-damaged sites.