A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex |
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Authors: | Sugasawa Kaoru Shimizu Yuichiro Iwai Shigenori Hanaoka Fumio |
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Affiliation: | Cellular Physiology Laboratory, RIKEN, The Institute of Physical and Chemical Research, 2-1 Hirosawa, Wako, 351-0198, Saitama, Japan. sugasawa@postman.riken.go.jp |
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Abstract: | The XPC-HR23B complex is involved in DNA damage recognition and the initiation of global genomic nucleotide excision repair (GG-NER). Our previous studies demonstrate that XPC-HR23B recognizes and binds DNA containing a helix distortion, regardless of the presence or absence of damaged bases. Here, we describe an extended analysis of the DNA binding specificity of XPC-HR23B using various defined DNA substrates. Although XPC-HR23B showed significantly higher affinity for single-stranded DNA than double-stranded DNA, specific secondary structures of DNA, involving a single- and double-strand junction, were strongly preferred by the complex. This indicates that the presence of bases, which cannot form normal Watson-Crick base pairs in double-stranded DNA, is a critical factor in determining the specificity of XPC-HR23B binding. A DNase I footprint analysis, using a looped DNA substrate, revealed that a single XPC-HR23B complex protected a distorted site in an asymmetrical manner, consistent with the preferred secondary structure. The specific binding of XPC-HR23B is undoubtedly an important molecular process, based on which NER machinery detects a wide variety of lesions that vary in terms of chemical structure during DNA repair. |
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