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Centrosomal localization of DNA damage checkpoint proteins
Author(s) -
Zhang Suisheng,
Hemmerich Peter,
Grosse Frank
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21195
Subject(s) - centrosome , microbiology and biotechnology , dna damage , biology , g2 m dna damage checkpoint , tubulin , mitosis , microtubule , chemistry , dna , biochemistry , cell cycle , cell cycle checkpoint , cell
During mitosis, the phosphatidylinositol‐3 (PI‐3) family‐related DNA damage checkpoint kinases ATM and ATR were found on the centrosomes of human cells. ATRIP, an interaction partner of ATR, as well as Chk1 and Chk2, the downstream targets of ATR or ATM, were also localized to the centrosomes. Surprisingly, the DNA‐PK inhibitor vanillin enhanced the level of ATM on centrosomes. Accordingly, DNA‐PKcs, the catalytic subunit of DNA‐PK, was also found on the centrosomes. Vanillin altered the phosphorylation of Chk2 in the centrosomes and in whole cell extracts. Nucleoplasmic ATM co‐immunoprecipitated with Ku70/86, the DNA binding subunits of DNA‐PK, while vanillin diminished this association. Vanillin did not affect microtubule polymerization at the centrosomes but, surprisingly, caused a transient enhancement of α‐tubulin foci in the nucleus. Interestingly, γ‐tubulin was also present in the nucleus and co‐immunoprecipitated with ATR or BRCA1. DNA damage led to a reduction of the mentioned checkpoint proteins on the centrosomes but increased the level of γ‐tubulin at this organelle. Taken together, these results indicate that DNA damage checkpoint proteins may control the formation of γ‐tubulin and/or the kinetics of microtubule formation at the centrosomes, and thereby couple them to the DNA damage response. J. Cell. Biochem. 101: 451–465, 2007. © 2006 Wiley‐Liss, Inc.