Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 22, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkx970
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [07022019]
- Platform for Drug Discovery, Informatics, and Structural Life Science from the Japan Agency for Medical Research and Development (AMED), Japan [16am0101033j0004]
- Japan Society for the Promotion of Science (JSPS) [16K07277]
- JSPS [26291005]
- Practical Research Project for Rare/Intractable Diseases from AMED
- KAKENHI from JSPS [15H05333, 14F04093]
- Special Coordination Funds for Promoting Science and Technology from the Japan Science and Technology Agency (JST)
- Japan Agency for Medical Research and Development
- Grants-in-Aid for Scientific Research [26291005, 17H00783, 16K07277, 14F04093, 16K15526, 15H05333] Funding Source: KAKEN
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Nucleotide excision repair is initiated by two different damage recognition subpathways, global genome repair (GGR) and transcription-coupled repair (TCR). In GGR, XPC detects DNA lesions and recruits TFIIH via interaction with the pleckstrin homology (PH) domain of TFIIH subunit p62. In TCR, an elongating form of RNA Polymerase II detects a lesion on the transcribed strand and recruits TFIIH by an unknown mechanism. Here, we found that the TCR initiation factor UVSSA forms a stable complex with the PH domain of p62 via a short acidic string in the central region of UVSSA, and determined the complex structure by NMR. The acidic string of UVSSA binds strongly to the basic groove of the PH domain by inserting Phe408 and Val411 into two pockets, highly resembling the interaction mechanism of XPC with p62. Mutational binding analysis validated the structure and identified residues crucial for binding. TCR activity was markedly diminished in UVSSA-deficient cells expressing UVSSA mutated at Phe408 or Val411. Thus, a common TFIIH recruitment mechanism is shared by UVSSA in TCR and XPC in GGR.
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