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Recombination Pathways (recombination + pathway)

Distribution by Scientific Domains

Life Sciences	80%

Selected Abstracts

Concerted action of plasmid maintenance functions: partition complexes create a requirement for dimer resolution

MOLECULAR MICROBIOLOGY, Issue 5 2006
Jean-Yves Bouet
Summary Partition of prokaryotic DNA requires formation of specific protein,centromere complexes, but an excess of the protein can disrupt segregation. The mechanisms underlying this destabilization are unknown. We have found that destabilization by the F plasmid partition protein, SopB, of plasmids carrying the F centromere, sopC, results from the capacity of the SopB,sopC partition complex to stimulate plasmid multimerization. Mutant SopBs unable to destabilize failed to increase multimerization. Stability of wild-type mini-F, whose ResD/rfsF site-specific recombination system enables it to resolve multimers to monomers, was barely affected by excess SopB. Destabilization of plasmids lacking the rfsF site was suppressed by recF, recO and recR, but not by recB, mutant alleles, indicating that multimerization is initiated from single-strand gaps. SopB did not alter the amounts or distribution of replication intermediates, implying that SopB,DNA complexes do not create single-strand gaps by blocking replication forks. Rather, the results are consistent with SopB,DNA complexes channelling gapped molecules into the RecFOR recombination pathway. We suggest that extended SopB,DNA complexes increase the likelihood of recombination between sibling plasmids by keeping them in close contact prior to SopA-mediated segregation. These results cast plasmid site-specific resolution in a new role , compensation for untoward consequences of partition complex formation. [source]

Assessing the link between BACH1/FANCJ and MLH1 in DNA crosslink repair

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010
Sharon B. Cantor
Abstract FANCJ (also known as BRIP1 or BACH1) is a DNA helicase that was originally identified by its direct interaction with the hereditary breast cancer protein, BRCA1. Similar to BRCA1, FANCJ function is essential for DNA repair and breast cancer suppression. FANCJ is also mutated in the cancer prone syndrome Fanconi anemia, for which patient cells are characterized by extreme sensitivity to agents that generate DNA interstand crosslinks. Unexpectedly, correction of the interstrand crosslink sensitivity of FANCJ-null patient cells did not require the FANCJ/BRCA1 interaction. Instead, FANCJ binding to the mismatch repair protein, MLH1 was required. Given this finding, we address the role of FANCJ and MLH1 in DNA crosslink processing and how their functions could be linked in checkpoint and/or recombination pathways. We speculate that after DNA crosslink processing and repair, the FANCJ/MLH1 interaction is critical for recovery and restart of replication. These ideas are considered and summarized in this review. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source]

Gene products encoded in the ninR region of phage , participate in Red-mediated recombination

GENES TO CELLS, Issue 4 2002
Trudee A. Tarkowski
Background:, The ninR region of phage , contains two recombination genes, orf (ninB) and rap (ninG), that were previously shown to have roles when the RecF and RecBCD recombination pathways of E. coli, respectively, operate on phage ,. Results:, When , DNA replication is blocked, recombination is focused at the termini of the virion chromosome. Deletion of the ninR region of , decreases the sharpness of the focusing without diminishing the overall rate of recombination. The phenotype is accounted for in large part by the deletion of rap and of orf. Mutation of the recJ gene of the host partially suppresses the Rap, phenotype. Conclusion: ninR functions Orf and Rap participate in Red recombination, the primary pathway operating when wild-type , grows lytically in rec+ cells. The ability of recJ mutation to suppress the Rap, phenotype indicates that RecJ exonuclease can participate in Red-mediated recombination, at least in the absence of Rap function. A model is presented for Red-mediated RecA-dependent recombination that includes these newly identified participants. [source]

Amplification of Hot DNA segments in Escherichia coli

MOLECULAR MICROBIOLOGY, Issue 6 2002
Ken-ichi Kodama
Summary In Escherichia coli, a replication fork blocking event at a DNA replication terminus (Ter) enhances homologous recombination at the nearby sister chromosomal region, converting the region into a recombination hotspot, Hot, site. Using a RNaseH negative (rnhA,) mutant, we identified eight kinds of Hot DNAs (HotA,H). Among these, enhanced recombination of three kinds of Hot DNAs (HotA,C) was dependent on fork blocking events at Ter sites. In the present study, we examined whether HotA DNAs are amplified when circular DNA (HotA plus a drug-resistance DNA) is inserted into the homologous region on the chromosome of a rnhA, mutant. The resulting HotA DNA transformants were analysed using pulsed-field gel electrophoresis, fluorescence in situ hybridization and DNA microarray technique. The following results were obtained: (i) HotA DNA is amplified by about 40-fold on average; (ii) whereas 90% of the cells contain about 6,10 copies of HotA DNA, the remaining 10% of cells have as many as several hundred HotA copies; and (iii) amplification is detected in all other Hot DNAs, among which HotB and HotG DNAs are amplified to the same level as HotA. Furthermore, HotL DNA, which is activated by blocking the clockwise oriC -starting replication fork at the artificially inserted TerL site in the fork-blocked strain with a rnhA+ background, is also amplified, but is not amplified in the non-blocked strain. From these data, we propose a model that can explain production of three distinct forms of Hot DNA molecules by the following three recombination pathways: (i) unequal intersister recombination; (ii) intrasister recombination, followed by rolling-circle replication; and (iii) intrasister recombination, producing circular DNA molecules. [source]

Induction of mitotic cell death in cancer cells by small interference RNA suppressing the expression of RecQL1 helicase

CANCER SCIENCE, Issue 1 2008
Kazunobu Futami
RecQL1 DNA helicase of the human RecQ helicase family participates in DNA repair and recombination pathways during cell-cycle replication. When we examined the effect of RecQL1 suppression on cell growth, we found that RecQL1 silencing by small interference RNA efficiently prevented proliferation of a wide range of cancer cells by inducing mitotic catastrophe and mitotic cell death. In contrast, such mitotic cell death was not seen in the growing normal fibroblasts used as controls, even if RecQL1 expression was fully downregulated. Our results support the hypothesis that endogenous DNA damage that occurs during DNA replication and remains unrepaired in cancer cells due to RecQL1 silencing induces cancer cell-specific mitotic catastrophe through a less-strict checkpoint in cancer cells than in normal cells. We speculate that normal cells are exempt from such mitotic cell death, despite slow growth, because cell-cycle progression is controlled strictly by a strong checkpoint system that detects DNA damage and arrests progression of the cell cycle until DNA damage is repaired completely. These results suggest that RecQL1 helicase is an excellent molecular target for cancer chemotherapy. (Cancer Sci 2008; 99: 71,80) [source]