scholarly journals Sgs1 Regulates Gene Conversion Tract Lengths and Crossovers Independently of Its Helicase Activity

2006 ◽  
Vol 26 (11) ◽  
pp. 4086-4094 ◽  
Author(s):  
Yi-Chen Lo ◽  
Kimberly S. Paffett ◽  
Or Amit ◽  
Jennifer A. Clikeman ◽  
Rosa Sterk ◽  
...  
Keyword(s):  
Gene Conversion ◽  
Genome Stability ◽  
Synthetic Lethality ◽  
Chromosome Loss ◽  
Helicase Activity ◽  
Tract Length ◽  
Independent Functions ◽  
Gene Conversion Tract ◽  
Conversion Tract

ABSTRACT RecQ helicases maintain genome stability and suppress tumors in higher eukaryotes through roles in replication and DNA repair. The yeast RecQ homolog Sgs1 interacts with Top3 topoisomerase and Rmi1. In vitro, Sgs1 binds to and branch migrates Holliday junctions (HJs) and the human RecQ homolog BLM, with Top3α, resolves synthetic double HJs in a noncrossover sense. Sgs1 suppresses crossovers during the homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Crossovers are associated with long gene conversion tracts, suggesting a model in which Sgs1 helicase catalyzes reverse branch migration and convergence of double HJs for noncrossover resolution by Top3. Consistent with this model, we show that allelic crossovers and gene conversion tract lengths are increased in sgs1Δ. However, crossover and tract length suppression was independent of Sgs1 helicase activity, which argues against helicase-dependent HJ convergence. HJs may converge passively by a “random walk,” and Sgs1 may play a structural role in stimulating Top3-dependent resolution. In addition to the new helicase-independent functions for Sgs1 in crossover and tract length control, we define three new helicase-dependent functions, including the suppression of chromosome loss, chromosome missegregation, and synthetic lethality in srs2Δ. We propose that Sgs1 has helicase-dependent functions in replication and helicase-independent functions in DSB repair by HR.

scholarly journals Multiple Heterologies Increase Mitotic Double-Strand Break-Induced Allelic Gene Conversion Tract Lengths in Yeast

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 665-679 ◽  
Author(s):  
Jac A Nickoloff ◽  
Douglas B Sweetser ◽  
Jennifer A Clikeman ◽  
Guru Jot Khalsa ◽  
Sarah L Wheeler
Keyword(s):  
Gene Conversion ◽  
Mismatch Repair ◽  
Frameshift Mutation ◽  
Strand Break ◽  
Double Strand Break ◽  
Chromosome Loss ◽  
Allelic Gene ◽  
Break Induced Replication ◽  
Gene Conversion Tract ◽  
Conversion Tract

Abstract Spontaneous and double-strand break (DSB)-induced allelic recombination in yeast was investigated in crosses between ura3 heteroalleles inactivated by an HO site and a +1 frameshift mutation, with flanking markers defining a 3.4-kbp interval. In some crosses, nine additional phenotypically silent RFLP mutations were present at ∼100-bp intervals. Increasing heterology from 0.2 to 1% in this interval reduced spontaneous, but not DSB-induced, recombination. For DSB-induced events, 75% were continuous tract gene conversions without a crossover in this interval; discontinuous tracts and conversions associated with a crossover each comprised ∼7% of events, and 10% also converted markers in unbroken alleles. Loss of heterozygosity was seen for all markers centromere distal to the HO site in 50% of products; such loss could reflect gene conversion, break-induced replication, chromosome loss, or G2 crossovers. Using telomere-marked strains we determined that nearly all allelic DSB repair occurs by gene conversion. We further show that most allelic conversion results from mismatch repair of heteroduplex DNA. Interestingly, markers shared between the sparsely and densely marked interval converted at higher rates in the densely marked interval. Thus, the extra markers increased gene conversion tract lengths, which may reflect mismatch repair-induced recombination, or a shift from restoration- to conversion-type repair.

scholarly journals Yeast intrachromosomal recombination: long gene conversion tracts are preferentially associated with reciprocal exchange and require the RAD1 and RAD3 gene products.

Genetics ◽  
1989 ◽  
Vol 123 (4) ◽  
pp. 683-694 ◽  
Author(s):  
A Aguilera ◽  
H L Klein
Keyword(s):  
Gene Conversion ◽  
Excision Repair ◽  
Dna Helicase ◽  
Repair Gene ◽  
Tract Length ◽  
Intrachromosomal Recombination ◽  
Recombination System ◽  
Mitotic Gene Conversion ◽  
Gene Conversion Tract ◽  
Conversion Tract

Abstract A yeast intrachromosomal recombination system based on an inverted repeat has been designed to examine mitotic gene conversion tract length and the association of crossing over with gene conversion as a function of the conversion tract length. Short conversion tracts are found to be preferentially noncrossover while conversion tracts longer than 1.16 kb show a 50% association with crossover. Mutation in the excision repair gene RAD1 leads to a reduction in conversion tracts of at least 1.16 kb and a reduction in crossovers associated with conversion, regardless of the length of the conversion tract. Mutation in the excision repair gene RAD3, which encodes a DNA helicase, also leads to a reduction in conversion tracts of at least 1.16 kb, but has no effect on the frequency of associated crossovers. The roles of RAD1 and RAD3 in recombination are discussed.

scholarly journals Length and distribution of meiotic gene conversion tracts and crossovers in Saccharomyces cerevisiae.

Genetics ◽  
1989 ◽  
Vol 123 (1) ◽  
pp. 69-80 ◽  
Author(s):  
R H Borts ◽  
J E Haber
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Conversion ◽  
Restriction Site ◽  
Apparent Difference ◽  
Yeast Saccharomyces Cerevisiae ◽  
Tract Length ◽  
Site Markers ◽  
Average Gene ◽  
Gene Conversion Tract ◽  
Conversion Tract

Abstract We have measured gene conversion tract length in strains of the yeast Saccharomyces cerevisiae containing three to six restriction site heterozygosities in a 9-kb interval. Tetrads containing a conversion were identified genetically by nonmendelian segregation of a marker in the middle of the interval. Gene conversions accompanied by a crossover have a tract length of 1.4 kb +/- 0.7 kb, which is indistinguishable from a tract length of 1.6 +/- 0.8 for conversions without an associated exchange. Among tetrads identified first as having a crossover in the interval, the average gene conversion tracts were apparently significantly shorter (0.71 +/- 1). We provide evidence that this apparent difference is due to the method of measuring conversion tracts and does not reflect a real difference in tract length. We also provide evidence that the number and position of restriction site markers alters the apparent distribution of the conversion tracts. More than ninety percent of the conversion tracts spanning three or more sites were continuous.

scholarly journals The Role of Blm Helicase in Homologous Recombination, Gene Conversion Tract Length, and Recombination Between Diverged Sequences inDrosophilamelanogaster

Genetics ◽  
2017 ◽  
Vol 207 (3) ◽  
pp. 923-933 ◽  
Author(s):  
Henry A. Ertl ◽  
Daniel P. Russo ◽  
Noori Srivastava ◽  
Joseph T. Brooks ◽  
Thu N. Dao ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Gene Conversion ◽  
Tract Length ◽  
Blm Helicase ◽  
Gene Conversion Tract ◽  
Conversion Tract ◽  
Recombination Gene

scholarly journals Meiotic gene conversion tract length distribution within the rosy locus of Drosophila melanogaster.

Genetics ◽  
1994 ◽  
Vol 137 (4) ◽  
pp. 1019-1026 ◽  
Author(s):  
A J Hilliker ◽  
G Harauz ◽  
A G Reaume ◽  
M Gray ◽  
S H Clark ◽  
...  
Keyword(s):  
Gene Conversion ◽  
Length Distribution ◽  
P Element ◽  
Base Pairs ◽  
Tract Length ◽  
Meiotic Gene ◽  
Co Conversion ◽  
Optimal Value ◽  
Gene Conversion Tract ◽  
Conversion Tract

Abstract Employing extensive co-conversion data for selected and unselected sites of known molecular location in the rosy locus of Drosophila. we determine the parameters of meiotic gene conversion tract length distribution. The tract length distribution for gene conversion events can be approximated by the equation P(L > or = n) = phi n where P is the probability that tract length (L) is greater than or equal to a specified number of nucleotides (n). From the co-conversion data, a maximum likelihood estimate with standard error for phi is 0.99717 +/- 0.00026, corresponding to a mean conversion tract length of 352 base pairs. (Thus, gene conversion tract lengths are sufficiently small to allow for extensive shuffling of DNA sequence polymorphisms within a gene). For selected site conversions there is a bias towards recovery of longer tracts. The distribution of conversion tract lengths associated with selected sites can be approximated by the equation P(L > or = n/ selected) = phi n(1 - n + n/phi), where P is now the probability that a selected site tract length (L) is greater than or equal to a specified number of nucleotides (n). For the optimal value of phi determined from the co-conversion analysis, the mean conversion tract length for selected sites is 706 base pairs. We discuss, in the light of this and other studies, the relationship between meiotic gene conversion and P element excision induced gap repair and determine that they are distinct processes defined by different parameters and, possibly, mechanisms.

Gene-conversion tract directionality is influenced by the chromosome environment

1998 ◽  
Vol 34 (4) ◽  
pp. 269-279 ◽  
Author(s):  
Jennifer Whelden Cho ◽  
Guru Jot Khalsa ◽  
Jac A. Nickoloff
Keyword(s):  
Gene Conversion ◽  
Gene Conversion Tract ◽  
Conversion Tract

scholarly journals Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yann Duroc ◽  
Rajeev Kumar ◽  
Lepakshi Ranjha ◽  
Céline Adam ◽  
Raphaël Guérois ◽  
...  
Keyword(s):  
Gene Conversion ◽  
Meiotic Recombination ◽  
Recombination Hotspots ◽  
Genome Wide ◽  
D Loop ◽  
Mismatch Recognition ◽  
Gene Conversion Tract ◽  
Gene Conversions ◽  
Conversion Tract

Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting crossover formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutLβ preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations.

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