Abstract
Gene conversion (conversion), the unidirectional transfer of DNA sequence information, occurs as a byproduct of recombinational repair of broken or damaged DNA molecules. Whereas excision repair processes replace damaged DNA by copying the complementary sequence from the undamaged strand of duplex DNA, recombinational mechanisms copy similar sequence, usually in another molecule, to replace the damaged sequence. In mitotic cells the other molecule is usually a sister chromatid, and the repair does not lead to genetic change. Less often a homologous chromosome or homologous sequence in an ectopic position is used. Conversion results from repair in two ways. First, if there was a double-strand gap at the site of a break, homologous sequence will be used as the template for synthesis to fill the gap, thus transferring sequence information in both strands. Second, recombinational repair uses complementary base pairing, and the heteroduplex molecule so formed is a source of conversion, both as heteroduplex and when donor (undamaged template) information is retained after correction of mismatched bases in heteroduplex. There are mechanisms that favour the use of sister molecules that must fail before ectopic homology can be used. Meiotic recombination events lead to the formation of crossovers required in meiosis for orderly segregation of pairs of homologous chromosomes. These events result from recombinational repair of programmed double-strand breaks, but in contrast with mitotic recombination, meiotic recombinational events occur predominantly between homologous chromosomes, so that transfer of sequence differences by conversion is very frequent. Transient recombination events that do not form crossovers form both between homologous chromosomes and between regions of ectopic homology, and leave their mark in the occurrence of frequent non-crossover conversion, including ectopic conversion.
Highlights
Gene conversion, called conversion, is the non-reciprocal transfer of genetic information between regions of DNA
Double-strand break-repair in mitotic cells is regulated by the action of cohesin to occur predominantly between sister molecules, reducing ectopic interactions
The numerous doublestrand break (DSB) made in early meiotic prophase open the cell to rampant recombination, and this recombination is constrained to favour interactions between homologues rather than sister molecules
Summary
Called conversion, is the non-reciprocal transfer of genetic information between regions of DNA. When one strand of a DNA molecule is damaged, repair mechanisms can replace damaged sequence by synthesizing the complement of the intact strand When both strands are damaged, for example by a doublestrand break (DSB) or a non-replicating lesion opposite to a single-strand gap, sequence information to repair the damage might be derived from homologous sequence in another DNA molecule or region. Programmed recombination, including crossing-over and conversion, plays major roles in the generation of antibody variability, and in meiosis where, in most eukaryotes, crossovers form the chiasmata that hold homologues together to ensure orderly segregation in the first meiotic division. Conversion accompanies these crossovers and leads to frequent recombination between allelic differences within genes. We do not expect that the mechanisms are fully understood, but these working models provide adequate structures on which to base our thinking
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