김미현 (UNIST / 기초과학연구원, 현 The Rockefeller University) | 한빛사논문 > 한빛사

한빛사논문

조회193

UNIST / 기초과학연구원, 현 The Rockefeller University

Nucleic Acids Res., Feb 05 2026, 54 (4) gkag078 | https://doi.org/10.1093/nar/gkag078 The interaction of XPG with TFIIH through p62 and XPD is required for the completion of nucleotide excision repair

Mihyun Kim ^1,2, Eunwoo Jeong ¹, Jiyoung Park ¹, Areetha D’Souza ^3,4, Miaw-Sheue Tsai ⁵, Chunli Yan ⁶, Ivaylo Ivanov ⁶, Walter J Chazin ^3,4,7, Hyun Suk Kim ^1,*, Orlando D. Schärer^1,2,8,9,*

¹Center for Genomic Integrity, Institute for Basic Science, Ulsan, Republic of Korea
²Department of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea
³Department of Biochemistry, Vanderbilt University, Nashville, TN 37240-7917, United States
⁴Center for Structural Biology, Vanderbilt University, Nashville, TN 37240-7917, United States
⁵Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States
⁶Department of Chemistry, Georgia State University, Atlanta, GA, United States
⁷Department of Chemistry, Vanderbilt University, Nashville, TN 37232-7917, United States
⁸Graduate School of Health Science and Technology, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea
⁹UPMC Hillman Cancer Center & Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213-1863, United States

^∗To whom correspondence should be addressed. : Orlando D. Schärer
Correspondence may also be addressed to Hyun Suk Kim.

Abstract

Nucleotide excision repair (NER) is the key pathway for the removal of DNA damage induced by UV irradiation and chemotherapeutic reagents. Protein-protein interactions are crucial for the dynamic and coordinated assembly of the proteins involved in DNA lesions. Here we focus on the role of interactions between the multi-subunit helicase/translocase complex TFIIH and the 3' endonuclease XPG. We show that XPG interacts with the p62 and XPD subunits of TFIIH through its long spacer region bridging its split active site. We show that interactions between three acidic regions of XPG and the Pleckstrin homology (PH) domain of p62 are of moderate importance for NER, while defects in the interactions with XPD fail to pull-down TFIIH and strongly reduce NER activity. These p62 and XPD interface mutations additively reduce NER activity. Unexpectedly, we show that these interactions did not impair the recruitment of XPG but instead were defective in the formation of a catalytically competent NER complex and in triggering the incision 5' to the lesion by ERCC1-XPF. Our studies provide fundamental insights into how interactions between TFIIH and XPG contribute to the NER pathway and, more generally, how modular protein-protein interactions control each step along the NER reaction coordinate.

논문정보

형식Research article
게재일2026년 02월 (BRIC 등록일 2026-02-09)
연구진국내(교신)+국외 연구진
분야 생명과학 > 분자생물학

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