The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

被引:40
作者
Yankiwski, V
Noonan, JP
Neff, NF
机构
[1] New York Blood Ctr, Mol Genet Lab, New York, NY 10021 USA
[2] Univ Med & Dent New Jersey, Grad Sch Biomed Sci, Newark, NJ 07107 USA
[3] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
关键词
D O I
10.1186/1471-2121-2-11
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Bloom syndrome is rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10) or PML (promyelocytic leukemia) nuclear bodies, where it associates with TOPIII alpha, and to the nucleolus. Results: This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. Conclusion: The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies.
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