FBS Colloquia No.393Human Cell Biology Group

Mechanisms of Removing Transcription-Blocking DNA Lesions: Functions and Interactions of Transcription-Coupled Nucleotide Excision Repair Factors

Nucleotide excision repair (NER) is a DNA repair mechanism that removes bulky helix-distorting lesions, such as UV-induced pyrimidine dimers. NER operates through two distinct sub-pathways based on how the DNA damage is recognized: global genome NER (GG-NER) and transcription-coupled NER (TC-NER). DNA lesions on the transcribed strand of active genes block the elongation by RNA polymerase II (RNAPII) and, if not repaired, can lead to cell death. TC-NER rapidly eliminates such transcription-blocking lesions, thereby preserving transcriptional activity and cellular viability. In TC-NER, stalled RNAPII at a lesion site recruits TC-NER factors (CSA, CSB, and UVSSA), which in turn facilitate the recruitment of core NER factors such as TFIIH and XPA. Although this recruitment process has been described, the precise molecular mechanisms by which the lesion is removed and transcription resumes remain largely unclear. In this colloquium, I will present research findings on the function of TC-NER factors and their interactions with RNAPII and other factors, and discuss their roles in TC-NER.