Biomedical subjects

A Sancar

Publications and source records attributed to A Sancar.

221 records · Page 13Linked to original sources

PubMedDate not supplied

Structure and function of the (A)BC excinuclease of Escherichia coli.

(A)BC excinuclease is the enzymatic activity resulting from the mixture of E. coli UvrA, UvrB and UvrC proteins with damaged DNA. This is a functional definition as new evidence suggests that the three proteins never associate in a ternary complex. The UvrA subunit associates with the UvrB subunit in the form of an A2B1 complex which, guided by UvrA's affinity for damaged DNA binds to a lesion in DNA and delivers the UvrB subunit to the damaged site. The UvrB-damaged DNA complex is extremely stable (t1/2 congruent to 100 min). The UvrC subunit, which has no specific affinity for damaged DNA, recognizes the UvrB-DNA complex with high specificity and the protein complex consisting of UvrB and UvrC proteins makes two incisions, the 8th phosphodiester bond 5' and the 5th phosphodiester bond 3' to the damaged nucleotide. (A)BC excinuclease recognizes DNA damage ranging from AP sites and thymine glycols to pyrimidine dimers, and the adducts of psoralen, cisplatinum, mitomycin C, 4-nitroquinoline oxide and interstrand crosslinks.

DNA Repair↗

PubMedDate not supplied

Properties and regulation of the UVRABC endonuclease.

This report summarizes the cloning of the uvrA, uvrB and uvrC genes of E. coli, the identification and isolation of the gene products, the regulation of the genes, and reconstitution of active UVRABC endonuclease from the individually isolated components.

Bacterial Proteins↗

PubMedDate not supplied

Nucleotide excision repair: from E. coli to man.

Nucleotide excision repair is both a 'wide spectrum' DNA repair pathway and the sole system for repairing bulky damages such as UV lesions or benzo[a]pyrene adducts. The mechanisms of nucleotide excision repair are known in considerable detail in Escherichia coli. Similarly, in the past 5 years important advances have been made towards understanding the biochemical mechanisms of excision repair in humans. The overall strategy of the repair is the same in the two species: damage recognition through a multistep mechanism involving a molecular matchmaker and an ATP-dependent unwinding of the damaged duplex; dual incisions at both sides of the lesion by two different nucleases, the 3' incision being followed by the 5'; removal of the damaged oligomer; resynthesis of the repair patch, whose length matches the gap size. Despite these similarities, the two systems are biochemically different and do not even share structural homology. E. coli excinuclease employs three proteins in contrast to 16/17 polypeptides in man; the excised fragment is longer in man: the procaryotic excinuclease is not able by itself to remove the excised oligomer whereas the human enzyme does. Thus, the excinuclease mode of action is well conserved throughout evolution, but not the biochemical tools: this represents a case of evolutionary convergence.

DNA Repair↗

PubMedDate not supplied

DNA repair.

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Animals↗

PubMedDate not supplied

Domainal evolution of a prokaryotic DNA repair protein and its relationship to active-transport proteins.

The ABC excision nuclease of Escherichia coli is an ATP-dependent DNA repair enzyme composed of three protein subunits, UvrA, UvrB and UvrC. The DNA sequences of all three genes have been reported. UvrA, the component that binds directly to the DNA, and UvrB, which attaches itself to the UvrA-DNA complex, both contain consensus sequences though to be diagnostic of ATP-binding sites, although the UvrC sequence does not. We now report that a computer analysis of the UvrA sequence has revealed an unusual series of internal duplications centering around putative metal-binding sites which may be involved in the interaction with DNA. We also find a strong evolutionary relationship to a family of prokaryotic membrane-associated active-transport proteins.

Amino Acid Sequence↗