A. Tremblay et al., A double-strand break in a chromosomal LINE element can be repaired by gene conversion with various endogenous LINE elements in mouse cells, MOL CELL B, 20(1), 2000, pp. 54-60
A double-strand break (DSB) in the mammalian genome has been shown to be a
very potent signal for the cell to activate repair processes. Two different
types of repair have been identified in mammalian cells. Broken ends can b
e rejoined with or without loss or addition of DNA or, alternatively, a hom
ologous template can be used to repair the break. For most genomic sequence
s the latter event would involve allelic sequences present on the sister ch
romatid or homologous chromosome. However, since more than 30% of our genom
e consists of repetitive sequences, these would have the option of using no
nallelic sequences for homologous repair, This could have an impact on the
evolution of these sequences and of the genome itself. We have designed an
assay to look at the repair of DSBs in LINE-1 (L1) elements which number 10
(5) copies distributed throughout the genome of all mammals, We introduced
into the genome of mouse epithelial cells an L1 element with an I-SceI endo
nuclease site. We induced DSBs at the I-SceI site and determined their mech
anism of repair. We found that in over 95% of cases, the DSBs were repaired
by an end-joining process. However, in almost 1% of cases, we found strong
evidence for repair involving gene conversion with various endogenous L1 e
lements, with some being used preferentially. In particular, the T-F family
and the L1Md-A2 subfamily, which are the most active in retrotransposition
, appeared to be contributing the most in this process. The degree of homol
ogy did not seem to be a determining factor in the selection of the endogen
ous elements used for repair but may be based instead on accessibility. Con
sidering their abundance and dispersion, gene conversion between repetitive
elements may be occurring frequently enough to be playing a role in their
evolution.