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| Item Type: | Article |
|---|---|
| Title: | Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair |
| Creators Name: | Luijsterburg, M.S. and von Bornstaedt, G. and Gourdin, A.M. and Politi, A.Z. and Mone, M.J. and Warmerdam, D.O. and Goedhart, J. and Vermeulen, W. and van Driel, R. and Hoefer, T. |
| Abstract: | To understand how multiprotein complexes assemble and function on chromatin, we combined quantitative analysis of the mammalian nucleotide excision DNA repair (NER) machinery in living cells with computational modeling. We found that individual NER components exchange within tens of seconds between the bound state in repair complexes and the diffusive state in the nucleoplasm, whereas their net accumulation at repair sites evolves over several hours. Based on these in vivo data, we developed a predictive kinetic model for the assembly and function of repair complexes. DNA repair is orchestrated by the interplay of reversible protein-binding events and progressive enzymatic modifications of the chromatin substrate. We demonstrate that faithful recognition of DNA lesions is time consuming, whereas subsequently, repair complexes form rapidly through random and reversible assembly of NER proteins. Our kinetic analysis of the NER system reveals a fundamental conflict between specificity and efficiency of chromatin-associated protein machineries and shows how a trade off is negotiated through reversibility of protein binding. |
| Keywords: | CHO Cells, Cultured Cells, DNA, DNA Damage, DNA Repair, DNA-Binding Proteins, Kinetics, Animals, Cricetinae, Cricetulus |
| Source: | Journal of Cell Biology |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Volume: | 189 |
| Number: | 3 |
| Page Range: | 445-463 |
| Date: | 3 May 2010 |
| Official Publication: | https://doi.org/10.1083/jcb.200909175 |
| PubMed: | View item in PubMed |
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