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Bioinformatic prediction of ultraviolet light mutagenesis sensitivity of human genes and a method for genetically engineering UVB resistance.

Lease KA, Papageorgio C - Cancer Inform (2011)

Bottom Line: Based on these observations, a bioinformatics approach was used to predict the vulnerability of human protein coding genes to UVB induced loss of function mutations.This data was used to evaluate in depth those genes associated with malignant melanoma.In addition, we demonstrate a method of genetically engineering genes that significantly improves resistance to UVB loss of function mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Education Office, One Hospital Drive, MA419, University of Missouri 65212, USA.

ABSTRACT
Living on earth, we are exposed to ultraviolet (UV) light as part of the solar radiation. UVB spectrum light exposure contributes to the development of skin cancer by interacting with pyrimidine pairs to create lesions called cyclobutane pyrimidine dimers. If these lesions are not removed by nucleotide excision repair, they often give rise to C to T transition mutations. Based on these observations, a bioinformatics approach was used to predict the vulnerability of human protein coding genes to UVB induced loss of function mutations. This data was used to evaluate in depth those genes associated with malignant melanoma. In addition, we demonstrate a method of genetically engineering genes that significantly improves resistance to UVB loss of function mutations.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of algorithm to assess UVB sensitivity. At left, boxes are drawn around UVB sites. Below the double stranded DNA is the single letter amino acid sequence for each codon of the upper strand. In the middle, nucleotides that have undergone mutation are shown in bold. The translated sequence is shown below the DNA. The BLOSUM62 substitution matrix score for each new amino acid compared to its original amino acid is shown at the bottom. At right, the sum of the negative BLOSUM62 scores is given as the total amino acid change score for this sequence.
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f1-cin-2011-121: Schematic representation of algorithm to assess UVB sensitivity. At left, boxes are drawn around UVB sites. Below the double stranded DNA is the single letter amino acid sequence for each codon of the upper strand. In the middle, nucleotides that have undergone mutation are shown in bold. The translated sequence is shown below the DNA. The BLOSUM62 substitution matrix score for each new amino acid compared to its original amino acid is shown at the bottom. At right, the sum of the negative BLOSUM62 scores is given as the total amino acid change score for this sequence.

Mentions: For each mutant, the BLOSUM62 amino acid substitution matrix was then used to quantitatively assess the consequence of the altered codon when translated.31 BLOSUM62 uses a log odds ratio score and awards negative scores to unfavorable amino acid substitutions.32 The sum score for all unfavorable mutations for a gene was computed to get an overall amino acid change score representing the UV susceptibility of the protein coding gene (Fig. 1). A perl script was written to carry out this algorithm.


Bioinformatic prediction of ultraviolet light mutagenesis sensitivity of human genes and a method for genetically engineering UVB resistance.

Lease KA, Papageorgio C - Cancer Inform (2011)

Schematic representation of algorithm to assess UVB sensitivity. At left, boxes are drawn around UVB sites. Below the double stranded DNA is the single letter amino acid sequence for each codon of the upper strand. In the middle, nucleotides that have undergone mutation are shown in bold. The translated sequence is shown below the DNA. The BLOSUM62 substitution matrix score for each new amino acid compared to its original amino acid is shown at the bottom. At right, the sum of the negative BLOSUM62 scores is given as the total amino acid change score for this sequence.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3091412&req=5

f1-cin-2011-121: Schematic representation of algorithm to assess UVB sensitivity. At left, boxes are drawn around UVB sites. Below the double stranded DNA is the single letter amino acid sequence for each codon of the upper strand. In the middle, nucleotides that have undergone mutation are shown in bold. The translated sequence is shown below the DNA. The BLOSUM62 substitution matrix score for each new amino acid compared to its original amino acid is shown at the bottom. At right, the sum of the negative BLOSUM62 scores is given as the total amino acid change score for this sequence.
Mentions: For each mutant, the BLOSUM62 amino acid substitution matrix was then used to quantitatively assess the consequence of the altered codon when translated.31 BLOSUM62 uses a log odds ratio score and awards negative scores to unfavorable amino acid substitutions.32 The sum score for all unfavorable mutations for a gene was computed to get an overall amino acid change score representing the UV susceptibility of the protein coding gene (Fig. 1). A perl script was written to carry out this algorithm.

Bottom Line: Based on these observations, a bioinformatics approach was used to predict the vulnerability of human protein coding genes to UVB induced loss of function mutations.This data was used to evaluate in depth those genes associated with malignant melanoma.In addition, we demonstrate a method of genetically engineering genes that significantly improves resistance to UVB loss of function mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Education Office, One Hospital Drive, MA419, University of Missouri 65212, USA.

ABSTRACT
Living on earth, we are exposed to ultraviolet (UV) light as part of the solar radiation. UVB spectrum light exposure contributes to the development of skin cancer by interacting with pyrimidine pairs to create lesions called cyclobutane pyrimidine dimers. If these lesions are not removed by nucleotide excision repair, they often give rise to C to T transition mutations. Based on these observations, a bioinformatics approach was used to predict the vulnerability of human protein coding genes to UVB induced loss of function mutations. This data was used to evaluate in depth those genes associated with malignant melanoma. In addition, we demonstrate a method of genetically engineering genes that significantly improves resistance to UVB loss of function mutations.

No MeSH data available.


Related in: MedlinePlus