Thermodynamic cooperativity and kinetic proofreading in DNA damage recognition and repair.
In humans UV-induced cyclobutane thymine dimers are excised by the joint action of six repair factors, RPA, XPA, XPC, TFIIH, XPG, and XPF.ERCC1. Yet, in vitro assays show that none of these six factors is capable of detectably discriminating thymine dimer-containing DNA from undamaged DNA. We show how two elementary principles in macromolecular recognition, (1). cooperativity and (2). kinetic proofreading, are utilized to confer specificity to the repair system where none exists at the individual repair factor level and enable human cells to excise thymine dimers with a physiologically relevant specificity and at a biologically acceptable rate.
Reardon
Joyce T
JT
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260, USA.
Sancar
Aziz
A
D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011740:Pyrimidine Dimers / Q000737:chemistry / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D014466:Ultraviolet Rays
D011740:Pyrimidine Dimers