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Title: Structure of the C-Terminal Half of UvrC Reveals an RNase H Endonuclease Domain with an Argonaute-like Catalytic Triad

Abstract

Removal and repair of DNA damage by the nucleotide excision repair pathway requires two sequential incision reactions, which are achieved by the endonuclease UvrC in eubacteria. Here, we describe the crystal structure of the C-terminal half of UvrC, which contains the catalytic domain responsible for 5' incision and a helix-hairpin-helix-domain that is implicated in DNA binding. Surprisingly, the 5' catalytic domain shares structural homology with RNase H despite the lack of sequence homology and contains an uncommon DDH triad. The structure also reveals two highly conserved patches on the surface of the protein, which are not related to the active site. Mutations of residues in one of these patches led to the inability of the enzyme to bind DNA and severely compromised both incision reactions. Based on our results, we suggest a model of how UvrC forms a productive protein-DNA complex to excise the damage from DNA.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930301
Report Number(s):
BNL-81006-2008-JA
Journal ID: ISSN 0261-4189; EMJODG; TRN: US200822%%1457
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: EMBO Journal; Journal Volume: 26
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CRYSTAL STRUCTURE; DAMAGE; DNA; DNA DAMAGES; ENDONUCLEASES; ENZYMES; EXCISION REPAIR; MUTATIONS; NUCLEOTIDES; REMOVAL; REPAIR; RESIDUES; SURFACES; national synchrotron light source

Citation Formats

Karakas,E., Truglio, J., Croteau, D., Rhau, B., Wang, L., Van Houten, B., and Kisker, C. Structure of the C-Terminal Half of UvrC Reveals an RNase H Endonuclease Domain with an Argonaute-like Catalytic Triad. United States: N. p., 2007. Web. doi:10.1038/sj.emboj.7601497.
Karakas,E., Truglio, J., Croteau, D., Rhau, B., Wang, L., Van Houten, B., & Kisker, C. Structure of the C-Terminal Half of UvrC Reveals an RNase H Endonuclease Domain with an Argonaute-like Catalytic Triad. United States. doi:10.1038/sj.emboj.7601497.
Karakas,E., Truglio, J., Croteau, D., Rhau, B., Wang, L., Van Houten, B., and Kisker, C. Mon . "Structure of the C-Terminal Half of UvrC Reveals an RNase H Endonuclease Domain with an Argonaute-like Catalytic Triad". United States. doi:10.1038/sj.emboj.7601497.
@article{osti_930301,
title = {Structure of the C-Terminal Half of UvrC Reveals an RNase H Endonuclease Domain with an Argonaute-like Catalytic Triad},
author = {Karakas,E. and Truglio, J. and Croteau, D. and Rhau, B. and Wang, L. and Van Houten, B. and Kisker, C.},
abstractNote = {Removal and repair of DNA damage by the nucleotide excision repair pathway requires two sequential incision reactions, which are achieved by the endonuclease UvrC in eubacteria. Here, we describe the crystal structure of the C-terminal half of UvrC, which contains the catalytic domain responsible for 5' incision and a helix-hairpin-helix-domain that is implicated in DNA binding. Surprisingly, the 5' catalytic domain shares structural homology with RNase H despite the lack of sequence homology and contains an uncommon DDH triad. The structure also reveals two highly conserved patches on the surface of the protein, which are not related to the active site. Mutations of residues in one of these patches led to the inability of the enzyme to bind DNA and severely compromised both incision reactions. Based on our results, we suggest a model of how UvrC forms a productive protein-DNA complex to excise the damage from DNA.},
doi = {10.1038/sj.emboj.7601497},
journal = {EMBO Journal},
number = ,
volume = 26,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}