Excellent Paper linking p21 expression and changes in Genome
dellaire at odyssee.net
Tue Mar 3 19:20:05 EST 1998
Take a look at this paper from PNAS showing a link between a tumor
supressor gene and global changes in chromosomal arrangements.
Pretty simple strategy and I think anyone with access to tumor supressor
cDNA's should be doing pilot experiments. This is going to be the start of
many such papers. The paper is quite short but the connotations are very
p21WAF-1 reorganizes the nucleus in tumor suppression
PNAS Vol. 95, Issue 3, 1131-1135, February 3, 1998
Gustavo Linares-Cruz et al.
Interphasic nuclear organization has a key function in genome biology.
We demonstrate that p21WAF-1, by influencing gene
expression and inducing chromosomal repositioning in tumor suppression,
plays a major role as a nuclear organizer.
Transfection of U937 tumor cells with p21WAF-1 resulted in expression of
the HUMSIAH (human seven in absentia
homologue), Rb, and Rbr-2 genes and strong suppression of the malignant
phenotype. p21WAF-1 drastically modified the
compartmentalization of the nuclear genome. DNase I genome exposure and
fluorescence in situ hybridization show,
respectively, a displacement of the sensitive sites to the periphery of
the nucleus and repositioning of chromosomes 13,
16, 17, and 21. These findings, addressing nuclear architecture
modulations, provide potentially significant perspectives for the
understanding of tumor suppression.
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