Repair of DNA-containing pyrimidine dimers
Ultraviolet light-induced pyrimidine dimers in DNA are recognized and repaired by a number of unique cellular surveillance systems. The most direct biochemical mechanism responding to this kind of genotoxicity involves direct photoreversal by flavin enzymes that specifically monomerize pyrimidine:pyrimidine dimers monophotonically in the presence of visible light. Incision reactions are catalyzed by a combined pyrimidine dimer DNA-glycosylase:apyrimidinic endonuclease found in some highly UV-resistant organisms. At a higher level of complexity, Escherichia coli has a uvr DNA repair system comprising the UvrA, UvrB, and UvrC proteins responsible for incision. There are several preincision steps governed by this pathway, which includes an ATP-dependent UvrA dimerization reaction required for UvrAB nucleoprotein formation. This complex formation driven by ATP binding is associated with localized topological unwinding of DNA. This same protein complex can catalyze an ATPase-dependent 5'----3'-directed strand displacement of D-loop DNA or short single strands annealed to a single-stranded circular or linear DNA. This putative translocational process is arrested when damaged sites are encountered. The complex is now primed for dual incision catalyzed by UvrC. The remainder of the repair process involves UvrD (helicase II) and DNA polymerase I for a coordinately controlled excision-resynthesis step accompanied by UvrABC turnover. Furthermore, it is proposed that levels of repair proteins can be regulated by proteolysis. UvrB is converted to truncated UvrB* by a stress-induced protease that also acts at similar sites on the E. coli Ada protein. Although UvrB* can bind with UvrA to DNA, it cannot participate in helicase or incision reactions. It is also a DNA-dependent ATPase.21 references.
- Research Organization:
- Johns-Hopkins Univ. School of Hygiene and Public Health, Baltimore, MD (USA)
- OSTI ID:
- 6769036
- Journal Information:
- FASEB J.; (United States), Journal Name: FASEB J.; (United States) Vol. 2:11; ISSN FAJOE
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACID ANHYDRASES
ATP
ATP-ASE
BACTERIA
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DNA
DNA REPAIR
DOCUMENT TYPES
ELECTROMAGNETIC RADIATION
ENZYMES
ESCHERICHIA COLI
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
HYDROLASES
MICROORGANISMS
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
PHOSPHOHYDROLASES
PYRIMIDINE DIMERS
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RECOVERY
REPAIR
REVIEWS
ULTRAVIOLET RADIATION