Intra-Arm and Inter-Arm Chromosome Intrachanges:
Tools for Probing the Geometry and Dynamics of Chromatin
Abstract.
Many radiation-produced, chromosome-type, exchange-type chromosomal
aberrations are intrachanges, i.e. involve only one chromosome. It
is assumed such intrachanges are formed by illegitimate reunion of
two DSBs (DNA double strand breaks) on the chromosome. The yield of
intra-arm intrachanges (acentric rings or paracentric inversions),
relative to that of inter-arm intrachanges (centric rings or
pericentric inversions), is larger than would occur if DSB production
and illegitimate reunion were spatially random. The excess of
intra-arm intrachanges is presumably due to proximity effects for
illegitimate reunions, i.e. enhancement of the intrachange
probability when two DSBs are formed close to one another. Radiation
track structure may also play a role. Using a polymer description
for chromatin geometry at large scales (> 2 Mb), and using two
alternate (rapid or slow motion) models for the way that DSBs move
after they are produced, theoretical estimates are given for
intrachange size distributions at low or high LET. The ratio of
intra-arm to inter-arm intrachanges is derived from the size
distribution and compared with data from the literature on centric
rings, inversions, interstitial deletions, and excess acentric
fragments. Proximity effects enhance yields of intra-arm relative to
inter-arm intrachanges, at least several fold and perhaps as much as
10-fold, compared to expectations based on spatial randomness. We
argue that further measurements of intra-arm and inter-arm
intrachanges would be informative about large-scale chromatin
structure and chromosome motion. Because inversions are more
frequent than randomness estimates would indicate, and are
transmissible to daughter cells, their size distribution could also
help characterize past exposure to high LET radiation.
Radiation Research 148, 330-339, 1997.
Rainer K. Sachs\(dg, David J. Brenner\(dd, Allen M.
Chen\(dg*, Philip Ha
hnfeldt\(sc, and Lynn R. Hlatky\(sc.
\(dgDept. Mathematics, University of California, Berkeley,
CA 920.
\(ddCenter for Radiological Research, Columbia University,
New York,
NY. *Lawrence Livermore National Laboratory, Livermore,
CA.
\(scJoint Center for Radiation Therapy, Harvard Medical
School,
Boston, MA.
intras