Very short patch (VSP) repair is a

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...

system that removes GT mismatches created by the

deamination Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of e ...

of 5-methylcytosine to

thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nu ...

. 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 Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain. Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (without regard to sequence), while many, typically called restriction endonucleases ...

occur in a variety of

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

. They work by cutting, or rather, making a nick in DNA if the

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

is mutated or damaged.

Function

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

VSR recognises a TG mismatched base pair, generated after spontaneous

methylated In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...

cytosines, and it creates a nick on a single strand by cleaving the

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

backbone on the 5' side of the thymine. Then

DNA Polymerase A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...

I removes the T and some nucleotides on the 3' strand and then resynthesises the patch. Additionally, GT mismatches can lead to C-to-T transition

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

if not repaired. VSR repairs the mismatches in favour of the G-containing strand. In ''Escherichia coli'', this

endonuclease Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain. Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (without regard to sequence), while many, typically called restriction endonucleases ...

nicks double-stranded DNA within the

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...

CT(AT)GN or NT(AT)GG next to the

thymidine Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. I ...

residue, which is mismatched to 2'-deoxyguanosine. The incision is mismatch-dependent and strand specific.

Structure

The

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

of VSR is similar to the core

of restriction endonucleases, which have a 3-layer alpha/beta/alpha topology. VSR has three aromatic residues ( Phe67, Trp68 and Trp86), which intercalate into the

major groove Major (commandant in certain jurisdictions) is a military rank of commissioned officer status, with corresponding ranks existing in many military forces throughout the world. When used unhyphenated and in conjunction with no other indicators ...

, bending the DNA and separating the two strands. The

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

domain stabilizes the interaction between the protein and the cleaved product, thereby protecting the nick from

DNA ligase DNA ligase is a specific type of enzyme, a ligase, () that facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond. It plays a role in repairing single-strand breaks in duplex DNA in living organ ...

until the arrival of DNA Polymerase I.

References

Protein families DNA repair {{genetics-stub