TITLE: Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia

AUTHOR CONTACT:
Elena I. Rugarli
National Neurological Institute, Milan, Italy
Phone: 39-02-23942614; Fax: 39-02-23942619; E-mail: rugarli@istituto-besta.it

View the PDF of this article at: https://www.the-jci.org/article.php?id=26210

ONCOLOGY
Chromosomal quality control keeps leukemia in check

Researchers from Tokyo Medical and Dental University have discovered how failure of a quality control checkpoint in the cell cycle during replication and division allows incorrectly re-joined breaks in chromosomal DNA to go unrepaired, causing leukemia. Their results will be reported online on December 15 in advance of print publication in the January 2006 issue of the Journal of Clinical Investigation.

After DNA replication (known as G2 phase in the cell cycle), but before mitosis (M phase), the enzyme topoisomerase II (Topo II) drives the momentary breaking and rejoining of double-stranded DNA, a process that controls DNA over- and under-winding. With nearly 6 feet of DNA rotating at high speed and being twisted and folded into a microscopic space during cell replication, our cells require several systems or "checkpoints" for interrupting the cell cycle if something goes wrong. In normal cells, the checkpoint kinase ATM (ataxia telangiectasia mutated) can halt the cell cycle and prompt any necessary DNA repair.

While etoposide, a Topo II inhibitor, has been used for over 20 years in the treatment of a variety of malignancies, an unfortunate complication of this treatment is increased DNA strand breaks,
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Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation
15-Dec-2005