scholarly journals Functional interactions between BLM and XRCC3 in the cell

2007 ◽  
Vol 179 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Makoto Otsuki ◽  
Masayuki Seki ◽  
Eri Inoue ◽  
Akari Yoshimura ◽  
Genta Kato ◽  
...  
Keyword(s):  
Sister Chromatid Exchanges ◽  
Methyl Methanesulfonate ◽  
Dna Topoisomerase ◽  
Homologous Chromosomes ◽  
Uv Sensitivity ◽  
Functional Interactions ◽  
Dna Damaging Agents ◽  
Repair Pathways ◽  
Chromatid Exchanges ◽  
Blm Gene

Bloom's syndrome (BS), which is caused by mutations in the BLM gene, is characterized by a predisposition to a wide variety of cancers. BS cells exhibit elevated frequencies of sister chromatid exchanges (SCEs), interchanges between homologous chromosomes (mitotic chiasmata), and sensitivity to several DNA-damaging agents. To address the mechanism that confers these phenotypes in BS cells, we characterize a series of double and triple mutants with mutations in BLM and in other genes involved in repair pathways. We found that XRCC3 activity generates substrates that cause the elevated SCE in blm cells and that BLM with DNA topoisomerase IIIα suppresses the formation of SCE. In addition, XRCC3 activity also generates the ultraviolet (UV)- and methyl methanesulfonate (MMS)–induced mitotic chiasmata. Moreover, disruption of XRCC3 suppresses MMS and UV sensitivity and the MMS- and UV-induced chromosomal aberrations of blm cells, indicating that BLM acts downstream of XRCC3.

Saccharomyces cerevisiae rad51 Mutants Are Defective in DNA Damage-Associated Sister Chromatid Exchanges but Exhibit Increased Rates of Homology-Directed Translocations

Genetics ◽  
2001 ◽  
Vol 158 (3) ◽  
pp. 959-972
Author(s):  
Michael Fasullo ◽  
Peter Giallanza ◽  
Zheng Dong ◽  
Cinzia Cera ◽  
Thomas Bennett
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Sister Chromatid ◽  
Sister Chromatid Exchanges ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Dna Damaging Agents ◽  
Break Induced Replication ◽  
Chromatid Exchanges

Abstract Saccharomyces cerevisiae Rad51 is structurally similar to Escherichia coli RecA. We investigated the role of S. cerevisiae RAD51 in DNA damage-associated unequal sister chromatid exchanges (SCEs), translocations, and inversions. The frequency of these rearrangements was measured by monitoring mitotic recombination between two his3 fragments, his3-Δ5′ and his3-Δ3′::HOcs, when positioned on different chromosomes or in tandem and oriented in direct or inverted orientation. Recombination was measured after cells were exposed to chemical agents and radiation and after HO endonuclease digestion at his3-Δ3′::HOcs. Wild-type and rad51 mutant strains showed no difference in the rate of spontaneous SCEs; however, the rate of spontaneous inversions was decreased threefold in the rad51 mutant. The rad51 null mutant was defective in DNA damage-associated SCE when cells were exposed to either radiation or chemical DNA-damaging agents or when HO endonuclease-induced double-strand breaks (DSBs) were directly targeted at his3-Δ3′::HOcs. The defect in DNA damage-associated SCEs in rad51 mutants correlated with an eightfold higher spontaneous level of directed translocations in diploid strains and with a higher level of radiation-associated translocations. We suggest that S. cerevisiae RAD51 facilitates genomic stability by reducing nonreciprocal translocations generated by RAD51-independent break-induced replication (BIR) mechanisms.

scholarly journals Meiotic sister chromatid exchanges are rare in C. elegans

2020 ◽  
Author(s):  
David E. Almanzar ◽  
Spencer G. Gordon ◽  
Ofer Rog
Keyword(s):  
Sister Chromatid ◽  
Homologous Chromosome ◽  
Sister Chromatid Exchanges ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
C Elegans ◽  
Sister Chromatids ◽  
Repair Template ◽  
Almost All ◽  
Chromatid Exchanges

AbstractSexual reproduction shuffles the parental genomes to generate new genetic combinations. To achieve that, the genome is subjected to numerous double-strand breaks, the repair of which involves two crucial decisions: repair pathway and repair template. Use of crossover pathways with the homologous chromosome as template exchanges genetic information and directs chromosome segregation. Crossover repair, however, can compromise the integrity of the repair template and is therefore tightly regulated. The extent to which crossover pathways are used during sister-directed repair is unclear, because the identical sister chromatids are difficult to distinguish. Nonetheless, indirect assays have led to the suggestion that inter-sister crossovers, or sister chromatid exchanges (SCEs), are quite common. Here we devised a technique to directly score physiological SCEs in the C. elegans germline using selective sister chromatid labeling with the thymidine analog 5-ethynyl-2’-deoxyuridine (EdU). Surprisingly, we find SCEs to be rare in meiosis, accounting for <2% of repair events. SCEs remain rare even when the homologous chromosome is unavailable, indicating that almost all sister-directed repair is channeled into noncrossover pathways. We identify two mechanisms that limit SCEs. First, sister-directed repair intermediates are efficiently inhibited by the RecQ helicase BLMHIM-6. Second, the Synaptonemal Complex–a conserved interface that promotes crossover repair– localizes between the homologous chromosomes and not the sister chromatids. Our data suggest that in C. elegans crossover pathways are only used to generate the single necessary link between the homologous chromosomes. Almost all other breaks, regardless of which repair template they use, are repaired by noncrossover pathways.

A novel frameshift mutation in BLM gene associated with high sister chromatid exchanges (SCE) in heterozygous family members

2014 ◽  
Vol 41 (11) ◽  
pp. 7373-7380 ◽  
Author(s):  
Ghada Ben Salah ◽  
Ikhlas Hadj Salem ◽  
Abderrahmen Masmoudi ◽  
Fakhri Kallabi ◽  
Hamida Turki ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Frameshift Mutation ◽  
Family Members ◽  
Sister Chromatid Exchanges ◽  
Chromatid Exchanges ◽  
Blm Gene
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