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3  structures 981  species 0  interactions 1075  sequences 8  architectures

Family: Vsr (PF03852)

Summary: DNA mismatch endonuclease Vsr

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This is the Wikipedia entry entitled "Very short patch repair". More...

Very short patch repair Edit Wikipedia article

Vsr
PDB 1cw0 EBI.jpg
Crystal structure of a very short patch repair (VSR) endonuclease in complex with duplex DNA
Identifiers
Symbol Vsr
Pfam PF03852
Pfam clan CL0236
InterPro IPR004603
SCOP 1vsr
SUPERFAMILY 1vsr

Very short patch (VSP) repair is a DNA repair system that removes GT mismatches created by the deamination of 5-methylcytosine to thymine. This system exists because the glycosylases which normally target deaminated bases cannot target thymine (it being one of the regular four bases in DNA).

The components of the system are MutS, which binds to the GT mismatch, the VSR endonuclease, which cuts the DNA, and MutL, which recruits the UvrD helicase.

VSR (very short patch repair) endonucleases occur in a variety of bacteria. They work by cutting, or rather, making a nick in DNA if the base pair is mutated or damaged.

Function[edit]

Mutations in the base pairs of DNA can be harmful to the organism. In particular, C to T mutations occur quite often due to methylation of cytosine. Hence, the VSR endonucleases have a function to protect the cell from damage caused by mutated DNA.

Mechanism[edit]

VSR recognises a TG mismatched base pair, generated after spontaneous deamination of methylated cytosines, and it creates a nick on a single strand by cleaving the phosphate backbone on the 5' side of the thymine.[1] Then DNA Polymerase I removes the T and some nucletides on the 3' strand and then resynthesises the patch. [2]

Additionally, GT mismatches can lead to C-to-T transition mutations if not repaired. VSR repairs the mismatches in favour of the G-containing strand. In Escherichia coli, this endonuclease nicks double-stranded DNA within the sequence CT(AT)GN or NT(AT)GG next to the thymidine residue, which is mismatched to 2'-deoxyguanosine.[3] The incision is mismatch-dependent and strand specific.

Structure[edit]

The structure of VSR is similar to the core structure of restriction endonucleases, which have a 3-layer alpha/beta/alpha topology.[4]

VSR has three aromatic residues (Phe67, Trp68 and Trp86), which intercalate into the major groove, bending the DNA and separating the two strands. The N-terminal domain stabilizes the interaction between the protein and the cleaved product, thereby protecting the nick from DNA ligase until the arrival of DNA Polymerase I.

References[edit]

  1. ^ Tsutakawa SE, Jingami H, Morikawa K (December 1999). "Recognition of a TG mismatch: the crystal structure of very short patch repair endonuclease in complex with a DNA duplex". Cell 99 (6): 615–23. PMID 10612397. 
  2. ^ Polosina YY, Cupples CG (2009). "Changes in the conformation of the Vsr endonuclease amino-terminal domain accompany DNA cleavage.". J Biochem 146 (4): 523–6. doi:10.1093/jb/mvp095. PMID 19556224. 
  3. ^ Bhagwat AS, Lieb M (June 2002). "Cooperation and competition in mismatch repair: very short-patch repair and methyl-directed mismatch repair in Escherichia coli". Mol. Microbiol. 44 (6): 1421–8. PMID 12067333. 
  4. ^ Bunting KA, Roe SM, Headley A, Brown T, Savva R, Pearl LH (March 2003). "Crystal structure of the Escherichia coli dcm very-short-patch DNA repair endonuclease bound to its reaction product-site in a DNA superhelix". Nucleic Acids Res. 31 (6): 1633–9. doi:10.1093/nar/gkg273. PMC 152875. PMID 12626704. 

This article incorporates text from the public domain Pfam and InterPro IPR004603

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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DNA mismatch endonuclease Vsr Provide feedback

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004603

This entry represents VSR (very short patch repair) endonucleases, which occur in a variety of bacteria. VSR recognises a TG mismatched base pair, generated after spontaneous deamination of methylated cytosines, and cleaves the phosphate backbone on the 5' side of the thymine [PUBMED:10612397]. GT mismatches can lead to C-to-T transition mutations if not repaired. VSR repairs the mismatches in favour of the G-containing strand. In Escherichia coli, this endonuclease nicks double-stranded DNA within the sequence CT(AT)GN or NT(AT)GG next to the thymidine residue, which is mismatched to 2'-deoxyguanosine [PUBMED:12067333]. The incision is mismatch-dependent and strand specific. The structure of VSR is similar to the core structure of restriction endonucleases, which have a 3-layer alpha/beta/alpha topology [PUBMED:12626704].

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Domain organisation

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  Seed
(7)
Full
(1075)
Representative proteomes NCBI
(738)
Meta
(161)
RP15
(76)
RP35
(158)
RP55
(204)
RP75
(248)
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  Seed
(7)
Full
(1075)
Representative proteomes NCBI
(738)
Meta
(161)
RP15
(76)
RP35
(158)
RP55
(204)
RP75
(248)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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Seed source: TIGRFAMs
Previous IDs: none
Type: Family
Author: TIGRFAMs, Griffiths-Jones SR
Number in seed: 7
Number in full: 1075
Average length of the domain: 73.40 aa
Average identity of full alignment: 49 %
Average coverage of the sequence by the domain: 47.87 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.6 20.9
Noise cut-off 20.4 20.5
Model length: 75
Family (HMM) version: 10
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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Vsr domain has been found. There are 3 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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