Mitotic recombination is suppressed by chromosomal divergence in hybrids of distantly related mouse strains

Mitotic recombination occurs with high frequency in humans(1,2) and mice(3) . It leads to loss of heterozygosity (LOH) at important gene loci and can c ause disease(4-7). However, the genetic modulators of mitotic recombination are not well understood. As recombination depends on a high level of nucle otide sequence homology(8-12), we postulate that the frequency of somatic v ariants derived from mitotic recombination should be diminished in progeny from crosses between strains of mice in which nucleotide sequences have div erged. Here we report that mitotic recombination is suppressed, to various degrees in different tissues, in hybrids of distantly related mouse strains . Reintroduction of greater chromosomal homology by backcrossing restores m itotic recombination in offspring. Thus, chromosomal divergence inhibits mi totic recombination and, consequently, may act as a modifier of cancer susc eptibility by limiting the rate of LOH. The suppression of mitotic recombin ation in some F-1 hybrids in which meiotic recombination persists indicates that these processes are differentially affected by chromosomal divergence .