Catalytic GIY-YIG domain of nucleotide excision repair endonucleases UvrC, Cho, and similar proteins
UvrC is essential for nucleotide excision repair (NER). The N-terminal catalytic GIY-YIG domain of UvrC (also known as Uri domain) is responsible for the 3' incision reaction and the C-terminal half of UvrC, consisting of an UvrB-binding domain (UvrBb), EndoV-like nuclease domain and a helix-hairpin-helix (HhH) DNA-binding domain, contains the residues involved in 5' incision. The N- and C-terminal regions are joined by a common Cys-rich domain containing four conserved Cys residues. Besides UvrC, protein Cho (UvrC homolog) serves as a second endonuclease in E. coli NER. Cho contains GIY-YIG motif followed by a Cys-rich region and shares sequence homology with the N-terminal half of UvrC. It is capable of incising the DNA at the 3' side of a lesion in the presence of the UvrA and UvrB proteins during NER. The C-terminal half of Cho is a unique uncharacterized domain, which is distinct from that of UvrC. Moreover, unlike UvrC, Cho does not require the UvrC-binding domain of UvrB for the 3' incision reaction, which might cause the shift in incision position and the difference in incision efficiencies between Cho and UvrC on different damaged substrates. Due to this, the range of NER in E. coli can be broadened by combining action of Cho and UvrC. This family also includes many uncharacterized epsilon proofreading subunits of DNA polymerase III, which have an additional N-terminal ExoIII domain and a 3'-5' exonuclease domain homolog, fused to an UvrC-like region or a Cho-like region. The UvrC-like region includes a GIY-YIG motif, followed by a Cys-rich region, and an UvrB-binding domain (UvrBb), but lacks the EndoV-like nuclease domain and the helix-hairpin-helix (HhH) DNA-binding domain. The Cho-like region consists of a GIY-YIG motif, followed by the Cys-rich region, and the unique uncharacterized domain presenting in the C-terminal half of Cho. Some family members may not carry the Cys-rich region. This family also includes a specific Cho-like protein from G. violaceus, which possesses only UvrBb domain at the C-terminus, but lacks the additional N-terminal ExoIII domain. The oother two remote homologs of UvrC, Bacillus-I and -II, are included in this family as well. Both of them contain a GIY-YIG domain, but no Cys-rich region. Moreover, the whole C-terminal region of Bacillus-I is replaces by an unknown domain, and Bacillus-II possesses another unknown N-terminal extension.
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