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Lee, Ja Yil
School of Life Sciences
Research Interests
  • Investigated eukaryotic homologous recombination.

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Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B

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Title
Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B
Author
Cheon, Na YoungKim, Hyun-SukYeo, Jung-EunScharer, Orlando D.Lee, Ja Yil
Issue Date
2019-09
Publisher
Oxford University Press
Citation
NUCLEIC ACIDS RESEARCH, v.47, no.16, pp.8337 - 8347
Abstract
DNA repair is critical for maintaining genomic integrity. Finding DNA lesions initiates the entire repair process. In human nucleotide excision repair (NER), XPC-RAD23B recognizes DNA lesions and recruits downstream factors. Although previous studies revealed the molecular features of damage identification by the yeast orthologs Rad4-Rad23, the dynamic mechanisms by which human XPC-RAD23B recognizes DNA defects have remained elusive. Here, we directly visualized the motion of XPC-RAD23B on undamaged and lesion-containing DNA using high-throughput single-molecule imaging. We observed three types of one-dimensional motion of XPC-RAD23B along DNA: diffusive, immobile and constrained. We found that consecutive AT-tracks led to increase in proteins with constrained motion. The diffusion coefficient dramatically increased according to ionic strength, suggesting that XPC-RAD23B diffuses along DNA via hopping, allowing XPC-RAD23B to bypass protein obstacles during the search for DNA damage. We also examined how XPC-RAD23B identifies cyclobutane pyrimidine dimers (CPDs) during diffusion. XPC-RAD23B makes futile attempts to bind to CPDs, consistent with low CPD recognition efficiency. Moreover, XPC-RAD23B binds CPDs in biphasic states, stable for lesion recognition and transient for lesion interrogation. Taken together, our results provide new insight into how XPC-RAD23B searches for DNA lesions in billions of base pairs in human genome.
URI
https://scholarworks.unist.ac.kr/handle/201301/27336
URL
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz629/5542879
DOI
10.1093/nar/gkz629
ISSN
0305-1048
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