期刊
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
卷 43, 期 10-11, 页码 509-516出版社
SPRINGER
DOI: 10.1007/s00249-014-0981-x
关键词
DNA damage; FRAP; Diffusion; DNA repair; WRN; BLM
类别
资金
- Danish Council for Independent research (DFF)
- CMOL through the Danish National Research Foundation
- Center for Healthy Aging
- Danish Ministry of Science
- National Institute of Aging, National Institutes of Health, USA
We have investigated the mobility of two EGFP-tagged DNA repair proteins, WRN and BLM. In particular, we focused on the dynamics in two locations, the nucleoli and the nucleoplasm. We found that both WRN and BLM use a DNA-scanning mechanism, with rapid binding-unbinding to DNA resulting in effective diffusion. In the nucleoplasm WRN and BLM have effective diffusion coefficients of 1.62 and 1.34 mu m(2)/s, respectively. Likewise, the dynamics in the nucleoli are also best described by effective diffusion, but with diffusion coefficients a factor of ten lower than in the nucleoplasm. From this large reduction in diffusion coefficient we were able to classify WRN and BLM as DNA damage scanners. In addition to WRN and BLM we also classified other DNA damage proteins and found they all fall into one of two categories. Either they are scanners, similar to WRN and BLM, with very low diffusion coefficients, suggesting a scanning mechanism, or they are almost freely diffusing, suggesting that they interact with DNA only after initiation of a DNA damage response.
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