X-Message-Number: 13080
Date: Wed, 12 Jan 2000 21:08:28 -0500
From: Jan Coetzee <>
Subject: Chromosomes get a break

                Chromosomes get a break
                Chromosomes break. This can damage cells severely and
lead to cancer. Cells
                have evolved sophisticated mechanisms for repairing such
damage, but the
                frequency with which chromosomes break has not been
fully appreciated. A
                recent study concludes that chromosomes are breaking
constantly. This
                conclusion results from experiments in which the
activity of chromosome
                repair enzymes was reduced. The research also suggests
that a nonhomologous
                DNA end joining pathway works full-time to repair the

Current Biology
Vol. 9, No. 24, 16/30 December 1999

 The nonhomologous DNA end joining pathway is important for
 chromosome stability in primary fibroblasts [Brief communication]
 Zarir E. Karanjawala, Ulf Grawunder, Chih-Lin Hsieh, Michael R.
 Current Biology 6 December 1999, 9:1501-1504.

     Abstract: There are two types of chromosome instability,
     structural and numerical, and these are important in cancer.
     Many structural abnormalities are likely to involve
     double-strand DNA (dsDNA) breaks. Nonhomologous
     DNA end joining (NHEJ) and homologous recombination
     are the major pathways for repairing dsDNA breaks. NHEJ
     is the primary pathway for repairing dsDNA breaks
     throughout the G0, G1 and early S phases of the cell cycle
     [1]. Ku86 and DNA ligase IV are two major proteins in the
     NHEJ pathway. We examined primary dermal fibroblasts
     from mice (wild type, Ku86+/-, Ku86-/-, and DNA ligase
     IV+/-) for chromosome breaks. Fibroblasts from Ku86+/- or
     DNA ligase IV+/- mice have elevated frequencies of
     chromosome breaks compared with those from wild-type
     mice. Fibroblasts from Ku86-/- mice have even higher
     levels of chromosome breaks. Primary pre-B cells from the
     same animals did not show significant accumulation of
     chromosome breaks. Rather the pre-B cells showed
     increased cell death. These studies demonstrate that
     chromosome breaks arise frequently and that NHEJ is
     required to repair this constant spontaneous damage.

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