Chromosome breakage and repair

Genetics

EMBO reports, 2005

Philosophical Transactions of the Royal Society B: Biological Sciences, 2004

Trends in Genetics, 1998

Cell, 1996

rate 25-30 times higher in MATa cells than in MAT␣ . MATa donor preference does not Rosenstiel Center and Department of Biology Brandeis University require the inactivation of HMR; in fact, when HML is deleted, MATa cells can efficiently recombine with HMR Waltham, Massachusetts 02254-9110 so that essentially all cells repair the HO-induced double-strand break at MAT .

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1981

Spontaneous interchange between the X chromosomes and the C(2L) autosomal compound in their centromeric regions was studied in y/XY,C(2L),C(2R) and In(1)dl-49÷BM1/xY, C(2L ),C(2R ) Drosophila melanogaster females. These females were mated with F(2L)/F(2L),C(2R) males. Interchange occurrence was recorded as the appearance of an F I individual with a half-translocation of either X. 2L or Y. 2L type. 37 interchanges were recovered in y/XY and 67 in In(1)/XY females. The majority of the interchanges were of meiotic origin. The interchanges were mainly C(2L)-XY; the most frequent type of halftranslocation was Y. 2L,dl-49+B M1. Inversion increased about 5-fold the interchange frequency. In the course of C(2L)-XY interchange, the other X chromosome and C(2R) compound regularly paired and disjoined. In y/XY females, 8 crossover half-translocations of meiotic origin were recovered.

Molecular and Cellular Biology, 1996

During homothallic switching of the mating-type (MAT) gene in Saccharomyces cerevisiae, a-or ␣-specific sequences are replaced by opposite mating-type sequences copied from one of two silent donor loci, HML␣ or HMRa. The two donors lie at opposite ends of chromosome III, approximately 190 and 90 kb, respectively, from MAT. MAT␣ cells preferentially recombine with HMR, while MATa cells select HML. The mechanisms of donor selection are different for the two mating types. MATa cells, deleted for the preferred HML gene, efficiently use HMR as a donor. However, in MAT␣ cells, HML is not an efficient donor when HMR is deleted; consequently, approximately one-third of HO HML␣ MAT␣ hmr⌬ cells die because they fail to repair the HO endonucleaseinduced double-strand break at MAT. MAT␣ donor preference depends not on the sequence differences between HML and HMR or their surrounding regions but on their chromosomal locations. Cloned HMR donors placed at three other locations to the left of MAT, on either side of the centromere, all fail to act as efficient donors.

Genetics

In order for two heterothallic MATa haploids of Saccharomyces cerevisiae to mate, one parent must apparently become, at least transiently, an a-like cell.

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1969

The current mutation theory required revision in the light of recent knowledge of the repairing system operative in a cell. The mechanism producing chromosome aberrations is discussed. The appearance of chromosome breakage is considered in relation to the activity of repairing systems in a cell, the dark-repair system in particular. Failure to understand how the breakage of one DNA strand in the chromosome structure is transferred to the other strand is the primary puzzle for interpreting the causes of chromosomal breakage, especially without DNA replication. This problem may be solved if one assumes that errors made by the repairing enzyme lead to the excision of the complementary region rather than of the region actually damaged, and that the gap made will remain and not be corrected by resynthesis. As a consequence, the second contact with repairing endonucleases will result in cutting of DNA in the vicinity of the damaged region which will cause breakage of the molecule. The same mechanism seems responsible for production of full and mosaic mutations as well as for translocation, inversion and deletion. The present-day mutation theory is going through a new stage. The classical molecular principles developed by J. WATSON, F. CRICK, E. FREESE and others, established the belief that mutation production comprises several stages. The problem of potential damage attracts widespread attention. The classification of potential damage 7 involving large experimental material reveals at least 3 classes: (~) short-lived changes fixed during exposure to a mutagen; (2) long-lived changes fixed within a cell cycle; (3) extra-long-lived changes persisting through a number of DNA syntheses. The molecular mechanism of potential damage is yet unknown. The studies by AUERBACH 2, SOBELS 2s, KIMBALL 19, RUSSELL 24 and others have contributed nmch to the development of our knowledge of potential damage. Among recent advances in the molecular theory of mutation is the finding of the effects of the repair system on the initial chromosome lesions. The study of these effects can prove helpful for the better understanding of the potential damage stage as well as getting insight into the mutation-fixation process. The mechanism of chromosome breakage and complete genie mutation production is still one of the main puz

Genetics, 1984

In yeast, meiotic recombination between a linear chromosome III and a haploid-viable circular chromosome will yield a dicentric, tandemly duplicated chromosome. Spores containing apparently intact dicentric chromosomes were recovered from tetrads with three viable spores. The spore containing the dicentric inherited URA3 (part of the recombinant DNA used to join regions near the ends of the chromosome into a circle) as well as HML, HMR and MAL2 (located near the two ends of a linear but deleted from the circle). The Ura+ Mal+ colonies were highly variegated, giving rise to as many as seven distinctly different stable ("healed") derivatives, some of which were Ura+ Mal+, others Ura+ Mal-and others Ura-Mal' . The colonies were also sectored for five markers (HIS4, LEUZ, CRYI, MAT and THR4) initially heterozygous in the tandemly duplicated dicentric chromosome.-Southern blot and genetic analyses have demonstrated that these stable derivatives arose from mitotic breakage of the dicentric chromosome, followed by one of several different healing events. The majority of the stable derivatives contained circular or linear chromosomes apparently resulting from homologous recombination between a broken chromosome end and a homologous region on the other end of the original dicentric duplicated chromosome. A smaller proportion of events resulted in apparently uniquely healed linear chromosomes in which the broken chromosome acquired a new telomere. In two instances we recovered chromosome 1 1 1 partially duplicated with a novel right end. We have also found one derivative that had also experienced rearrangement of repeated DNA sequences found adjacent to yeast telomeres. ROKEN chromosomes, lacking a telomere, are mitotically unstable in both B maize (MCCLINTOCK 194 1) and the yeast Saccharomyces cerevisiae (MC-CUSKER and HABER 198 1 ; WEIFFENBACH and HABER 198 1 ; HABER, . In both organisms, broken chromosomes can become "healed" (that is, mitotically stable). In maize, such healing events often involved chromosomal rearrangements that in essence allowed a broken chromosome to acquire a new telomere by translocation involving another, nonhomologous chromosome. In other cases, MCCLINTOCK (1 94 1) observed terminally deficient chromosomes in which the origin of the telomeric region could not be determined.