20. In order to study the transcription factor TFIIH. It was cloned from a large number of human subjects. Surprisingly, the subject having mutation in TFIIH, also showed defects in their DNA repair system
Given below are the explanations:
A DNA damage is always associated with transcription inhibition.
B TFIIH has no role in DNA repair
C In mammalian system, TFIIH plays an active role in transcription coupled DNA repair process
D. Because of mutation in TFIIH, transcription initiation is inhibited and incompletely synthesized mRNAs remain attached to the template DNA leading to DNA damage.
Choose the correct answer.
(1)  A and B            (2) C only
(3) B and D         (4) D only

TFIIH Mutation Impact on Transcription and DNA Repair

Question Recap:

Given the statements about TFIIH mutation effects:

A. DNA damage is always associated with transcription inhibition.
B. TFIIH has no role in DNA repair.
C. In mammalian systems, TFIIH plays an active role in transcription-coupled DNA repair process.
D. Because of mutation in TFIIH, transcription initiation is inhibited and incompletely synthesized mRNAs remain attached to the template DNA leading to DNA damage.

Choose the correct answer:
(1) A and B
(2) C only
(3) B and D
(4) D only

Correct Answer:

(2) C only

Detailed Explanation:

Role of TFIIH in Transcription and DNA Repair
TFIIH is a multifunctional protein complex essential for both transcription initiation and nucleotide excision repair (NER), particularly transcription-coupled NER (TC-NER). It has helicase activities (via XPB and XPD subunits) that open DNA around transcription start sites and DNA lesions, enabling both transcription initiation and DNA repair processes.

• TFIIH is part of the pre-initiation complex in transcription, helping to open the promoter DNA and phosphorylate RNA Polymerase II to start transcription.

• In DNA repair, TFIIH unwinds damaged DNA around lesions, facilitating the recruitment of downstream repair proteins to excise and repair bulky DNA damage, especially in the TC-NER pathway.

Why Statement C is Correct:
Mammalian TFIIH plays an active and crucial role in transcription-coupled DNA repair by recognizing stalled RNA Polymerase II at DNA lesions and promoting repair. This is well established by studies showing TFIIH recruitment to lesions and its helicase activity opening DNA for repair enzymes.

Why Statements A, B, and D are Incorrect:

• A: DNA damage is always associated with transcription inhibition.
  This is an oversimplification. While DNA damage can cause transient transcription inhibition due to stalling of RNA Pol II, cells have mechanisms like TC-NER to resume transcription after repair. DNA damage does not always permanently inhibit transcription.

• B: TFIIH has no role in DNA repair.
  This is false. TFIIH is a key factor in NER and TC-NER pathways, directly involved in DNA repair.

• D: Because of mutation in TFIIH, transcription initiation is inhibited and incompletely synthesized mRNAs remain attached to the template DNA leading to DNA damage.
  This is not supported by evidence. Mutations in TFIIH impair transcription initiation and DNA repair, but there is no known mechanism where incompletely synthesized mRNAs physically remain attached to DNA causing DNA damage. The DNA damage observed is due to defective repair, not mRNA retention.

Summary

Conclusion

TFIIH is a critical factor linking transcription and DNA repair. Mutations in TFIIH impair both transcription initiation and nucleotide excision repair, especially transcription-coupled repair, causing defects in DNA repair systems in affected individuals. The only correct explanation among the options is C.