Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34934
Jiao, R; Harrigan, J A; Shevelev, I; Dietschy, T; Selak, N; Indig, F E; Piotrowski, J; Janscak, P; Bohr, V A; Stagljar, I (2007). The Werner syndrome protein is required for recruitment of chromatin assembly factor 1 following DNA damage. Oncogene, 26(26):3811-3822.
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The Werner syndrome protein (WRN) and chromatin assembly factor 1 (CAF-1) are both involved in the maintenance of genome stability. In response to DNA-damaging signals, both of these proteins relocate to sites where DNA synthesis occurs. However, the interaction between WRN and CAF-1 has not yet been investigated. In this report, we show that WRN interacts physically with the largest subunit of CAF-1, hp150, in vitro and in vivo. Although hp150 does not alter WRN catalytic activities in vitro, and the chromatin assembly activity of CAF-1 is not affected in the absence of WRN in vivo, this interaction may have an important role during the cellular response to DNA replication fork blockage and/or DNA damage signals. In hp150 RNA-mediated interference (RNAi) knockdown cells, WRN partially formed foci following hydroxyurea (HU) treatment. However, in the absence of WRN, hp150 did not relocate to form foci following exposure to HU and ultraviolet light. Thus, our results demonstrate that WRN responds to DNA damage before CAF-1 and suggest that WRN may recruit CAF-1, via interaction with hp150, to DNA damage sites during DNA synthesis.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research|
07 Faculty of Science > Institute of Molecular Cancer Research
|DDC:||570 Life sciences; biology|
|Deposited On:||16 Jul 2010 12:00|
|Last Modified:||11 Dec 2012 08:26|
|Publisher:||Nature Publishing Group|
|Free access at:||Publisher DOI. An embargo period may apply.|
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