related to degree

• Rosenblum, Jonathan, Ph.D. in Chemistry, Scripps Research 1991 - 1996

authors

• Rosenblum, Jonathan
• Gilula, N. B.
• Lerner, Richard

publication date

• 1996

journal

• Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

• We report a previously unappreciated property of the signals that target organelle-specific proteins to their subcellular sites of action. Such targeting sequences are shown to be polymorphic. We discovered this polymorphism when we cloned the mitochondrial manganese-containing superoxide dismutase from cell lines of normal individuals and patients with genetic diseases of premature aging and compared their sequences to each other and to those previously reported. The polymorphism consists of a single nucleotide change in the region of the DNA that encodes the signal sequence such that either an alanine or valine is present. Subsequently, eight cell lines were analyzed and all three possible combinations of the two signal sequences were observed. Such signal sequence polymorphisms could result in diseases of distribution, where essential proteins are not properly targeted, thereby leading to absolute or relative deficiencies of critical enzymes within specific cellular compartments. Progeria and related syndromes may be diseases of distribution.

subject areas

• Base Sequence
• Cell Line
• Cloning, Molecular
• Cockayne Syndrome
• DNA Primers
• Humans
• Molecular Sequence Data
• Mutation
• Polymerase Chain Reaction
• Polymorphism, Genetic
• Progeria
• Protein Sorting Signals
• Superoxide Dismutase
• Werner Syndrome

International Standard Serial Number (ISSN)

• 0027-8424

Digital Object Identifier (DOI)

• 10.1073/pnas.93.9.4471

PubMed ID

• 8633092

start page

• 4471

end page

• 4473

volume

• 93

issue

• 9