Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation

2006 ◽  
Vol 34 (4) ◽  
pp. 523-525 ◽  
Author(s):  
S. Keeney ◽  
M.J. Neale
Keyword(s):  
Homologous Recombination ◽  
Protein Kinases ◽  
Chromosome Segregation ◽  
Protein Interactions ◽  
Meiotic Recombination ◽  
Double Strand Breaks ◽  
Protein Protein Interactions ◽  
Dna Double Strand Breaks ◽  
Early Step ◽  
Strand Breaks

Homologous recombination is essential for accurate chromosome segregation during meiosis in most sexual organisms. Meiotic recombination is initiated by the formation of DSBs (DNA double-strand breaks) made by the Spo11 protein. We review here recent findings pertaining to protein–protein interactions important for DSB formation, the mechanism of an early step in the processing of Spo11-generated DSBs, and regulation of DSB formation by protein kinases.

scholarly journals Conserved HORMA domain-containing protein Hop1 stabilizes interaction between proteins of meiotic DNA break hotspots and chromosome axis

2019 ◽  
Vol 47 (19) ◽  
pp. 10166-10180 ◽  
Author(s):  
Ryo Kariyazono ◽  
Arisa Oda ◽  
Takatomi Yamada ◽  
Kunihiro Ohta
Keyword(s):  
Fission Yeast ◽  
Protein Interactions ◽  
Meiotic Recombination ◽  
Protein Protein Interactions ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Multiple Protein ◽  
Chromatin Immunoprecipitation Sequencing ◽  
The One ◽  
Chromosome Axis

Abstract HORMA domain-containing proteins such as Hop1 play crucial regulatory roles in various chromosomal functions. Here, we investigated roles of the fission yeast Hop1 in the formation of recombination-initiating meiotic DNA double strand breaks (DSBs). Meiotic DSB formation in fission yeast relies on multiple protein-protein interactions such as the one between the chromosome axial protein Rec10 and the DSB-forming complex subunit Rec15. Chromatin immunoprecipitation sequencing demonstrated that Hop1 is colocalized with both Rec10 and Rec15, and we observed physical interactions of Hop1 to Rec15 and Rec10. These results suggest that Hop1 promotes DSB formation by interacting with both axis components and the DSB-forming complex. We also show that Hop1 binding to DSB hotspots requires Rec15 and Rec10, while Hop1 axis binding requires Rec10 only, suggesting that Hop1 is recruited to the axis via Rec10, and to hotspots by hotspot-bound Rec15. Furthermore, we introduced separation-of-function Rec10 mutations, deficient for interaction with either Rec15 or Hop1. These single mutations and hop1Δ conferred only partial defects in meiotic recombination, while the combining the Rec15-binding-deficient rec10 mutation with hop1Δ synergistically reduced meiotic recombination, at least at a model hotspot. Taken together, Hop1 likely functions as a stabilizer for Rec15–Rec10 interaction to promote DSB formation.

scholarly journals Activation of meiotic recombination by nuclear import of the DNA break hotspot-determining complex in fission yeast

2021 ◽  
Vol 134 (4) ◽  
pp. jcs253518 ◽  
Author(s):  
Mélody Wintrebert ◽  
Mai-Chi Nguyen ◽  
Gerald R. Smith
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Recombination ◽  
High Specificity ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Nuclear Entry ◽  
Strand Breaks ◽  
Protein Complex Formation ◽  
Complex Process ◽  
Localization Signal

ABSTRACTMeiotic recombination forms crossovers important for proper chromosome segregation and offspring viability. This complex process involves many proteins acting at each of the multiple steps of recombination. Recombination initiates by formation of DNA double-strand breaks (DSBs), which in the several species examined occur with high frequency at special sites (DSB hotspots). In Schizosaccharomyces pombe, DSB hotspots are bound with high specificity and strongly activated by linear element (LinE) proteins Rec25, Rec27 and Mug20, which form colocalized nuclear foci with Rec10, essential for all DSB formation and recombination. Here, we test the hypothesis that the nuclear localization signal (NLS) of Rec10 is crucial for coordinated nuclear entry after forming a complex with other LinE proteins. In NLS mutants, all LinE proteins were abundant in the cytoplasm, not the nucleus; DSB formation and recombination were much reduced but not eliminated. Nuclear entry of limited amounts of Rec10, apparently small enough for passive nuclear entry, can account for residual recombination. LinE proteins are related to synaptonemal complex proteins of other species, suggesting that they also share an NLS, not yet identified, and undergo protein complex formation before nuclear entry.This article has an associated First Person interview with Mélody Wintrebert, joint first author of the paper.

scholarly journals SPO16 binds SHOC1 to promote homologous recombination and crossing-over in meiotic prophase I

2019 ◽  
Vol 5 (1) ◽  
pp. eaau9780 ◽  
Author(s):  
Qianting Zhang ◽  
Shu-Yan Ji ◽  
Kiran Busayavalasa ◽  
Chao Yu
Keyword(s):  
Homologous Recombination ◽  
Meiotic Recombination ◽  
Double Strand Breaks ◽  
Crossing Over ◽  
Dna Double Strand Breaks ◽  
Dsb Repair ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Recombination Nodules ◽  
Evolutionarily Conserved

Segregation of homologous chromosomes in meiosis I is tightly regulated by their physical links, or crossovers (COs), generated from DNA double-strand breaks (DSBs) through meiotic homologous recombination. In budding yeast, three ZMM (Zip1/2/3/4, Mer3, Msh4/5) proteins, Zip2, Zip4, and Spo16, form a “ZZS” complex, functioning to promote meiotic recombination via a DSB repair pathway. Here, we identified the mammalian ortholog of Spo16, termed SPO16, which interacts with the mammalian ortholog of Zip2 (SHOC1/MZIP2), and whose functions are evolutionarily conserved to promote the formation of COs. SPO16 localizes to the recombination nodules, as SHOC1 and TEX11 do. SPO16 is required for stabilization of SHOC1 and proper localization of other ZMM proteins. The DSBs formed in SPO16-deleted meiocytes were repaired without COs formation, although synapsis is less affected. Therefore, formation of SPO16-SHOC1 complex–associated recombination intermediates is a key step facilitating meiotic recombination that produces COs from yeast to mammals.

scholarly journals Activation of meiotic recombination by nuclear import of the DNA break hotspot-determining complex

2020 ◽  
Author(s):  
Mélody Wintrebert ◽  
Mai-Chi Nguyen ◽  
Gerald R. Smith
Keyword(s):  
Complex Formation ◽  
Chromosome Segregation ◽  
Meiotic Recombination ◽  
High Specificity ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Nuclear Entry ◽  
Strand Breaks ◽  
Protein Complex Formation ◽  
Localization Signal

AbstractMeiotic recombination forms crossovers important for proper chromosome segregation and viability of offspring. This process involves many proteins acting at each of the multiple steps of recombination. Recombination is initiated by formation of DNA double-strand breaks (DSBs), which in the several species examined often occur with high frequency at special sites (DSB hotspots). In the fission yeast Schizosaccharomyces pombe DSB hotspots are bound with high specificity and activated by linear element (LinE) proteins Rec25, Rec27, and Mug20 which form co-localized nuclear foci with Rec10, essential for all DSB formation and recombination. Here, we identify Rec10’s nuclear localization signal (NLS) and show it is important for coordinated nuclear entry after complex-formation with other LinE proteins. In NLS mutants, recombination is much reduced but not eliminated; nuclear entry of limited amounts of Rec10 can account for the residual recombination. LinEs are related to synaptonemal complex proteins of other species, suggesting that they also may share an as-yet-unidentified NLS and protein complex-formation before nuclear entry.

scholarly journals FIGL1 and its novel partner FLIP form a conserved complex that regulates homologous recombination

2017 ◽  
Author(s):  
Joiselle Blanche Fernandes ◽  
Marine Duhamel ◽  
Mathilde Séguéla-Arnaud ◽  
Nicole Froger ◽  
Chloé Girard ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Chromosome Segregation ◽  
Double Strand Breaks ◽  
Genetic Screens ◽  
Dna Double Strand Breaks ◽  
Interacting Protein ◽  
Strand Breaks ◽  
Protein Protein Interaction ◽  
Meiotic Crossover ◽  
Strand Invasion

AbstractHomologous recombination is central to repair DNA double-strand breaks (DSB), either accidently arising in mitotic cells or in a programed manner at meiosis. Crossovers resulting from the repair of meiotic breaks are essential for proper chromosome segregation and increase genetic diversity of the progeny. However, mechanisms regulating CO formation remain elusive. Here, we identified through protein-protein interaction and genetic screens FIDGETIN-LIKE-1 INTERACTING PROTEIN (FLIP) as a new partner of the previously characterized anti-crossover factor FIDGETIN-LIKE-1 (FIGL1) in Arabidopsis thaliana. We showed that FLIP limits meiotic crossover together with FIGL1. Further, FLIP and FIGL1 form a protein complex conserved from Arabidopsis to Human. FIGL1 interacts with the recombinases RAD51 and DMC1, the enzymes that catalyze the DNA stand exchange step of homologous recombination. Arabidopsis flip mutants recapitulates the figl1 phenotype, with enhanced meiotic recombination associated with change in DMC1 dynamics. Our data thus suggest that FLIP and FIGL1 form a conserved complex that regulates the crucial step of strand invasion in homologous recombination.

scholarly journals Fission Yeast Cut8 Is Required for the Repair of DNA Double-Strand Breaks, Ribosomal DNA Maintenance, and Cell Survival in the Absence of Rqh1 Helicase

2006 ◽  
Vol 27 (5) ◽  
pp. 1558-1567 ◽  
Author(s):  
Stephen E. Kearsey ◽  
Abigail L. Stevenson ◽  
Takashi Toda ◽  
Shao-Win Wang
Keyword(s):  
Homologous Recombination ◽  
Chromosome Segregation ◽  
Strand Break ◽  
Dna Helicase ◽  
Double Strand Breaks ◽  
Proper Function ◽  
Checkpoint Control ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Dna Maintenance

ABSTRACT Schizosaccharomyces pombe Rqh1 is a member of the RecQ DNA helicase family. Members of this protein family are mutated in cancer predisposition diseases, causing Bloom's, Werner, and Rothmund-Thomson syndromes. Rqh1 forms a complex with topoisomerase III and is proposed to process or disrupt aberrant recombination structures that arise during S phase to allow proper chromosome segregation during mitosis. Intriguingly, in the absence of Rqh1, processing of these structures appears to be dependent on Rad3 (human ATR) in a manner that is distinct from its role in checkpoint control. Here, we show that rad3 rqh1 mutants are normally committed to a lethal pathway of DNA repair requiring homologous recombination, but blocking this pathway by Rhp51 inactivation restores viability. Remarkably, viability is also restored by overexpression of Cut8, a nuclear envelope protein involved in tethering and proper function of the proteasome. In keeping with a recently described function of the proteasome in the repair of DNA double-strand breaks, we found that Cut8 is also required for DNA double-strand break repair and is essential for proper chromosome segregation in the absence of Rqh1, suggesting that these proteins might function in a common pathway in homologous recombination repair to ensure accurate nuclear division in S. pombe.

scholarly journals End-resection at DNA double-strand breaks in the three domains of life

2013 ◽  
Vol 41 (1) ◽  
pp. 314-320 ◽  
Author(s):  
John K. Blackwood ◽  
Neil J. Rzechorzek ◽  
Sian M. Bray ◽  
Joseph D. Maman ◽  
Luca Pellegrini ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Domains Of Life ◽  
Strand Invasion ◽  
End Resection

During DNA repair by HR (homologous recombination), the ends of a DNA DSB (double-strand break) must be resected to generate single-stranded tails, which are required for strand invasion and exchange with homologous chromosomes. This 5′–3′ end-resection of the DNA duplex is an essential process, conserved across all three domains of life: the bacteria, eukaryota and archaea. In the present review, we examine the numerous and redundant helicase and nuclease systems that function as the enzymatic analogues for this crucial process in the three major phylogenetic divisions.

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