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  1. Article: De novo deletions and duplications at recombination hotspots in mouse germlines

    Lukaszewicz, Agnieszka / Lange, Julian / Keeney, Scott / Jasin, Maria

    Cell. 2021 Nov. 24, v. 184, no. 24

    2021  

    Abstract: Numerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here, we uncover a distinct type of mutational event in which deletions form via joining of ends from two ... ...

    Abstract Numerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here, we uncover a distinct type of mutational event in which deletions form via joining of ends from two closely spaced DSBs (double cuts) within a single hotspot or at adjacent hotspots on the same or different chromatids. Deletions occur in normal meiosis but are much more frequent when DSB formation is dysregulated in the absence of the ATM kinase. Events between chromosome homologs point to multi-chromatid damage and aborted gap repair. Some deletions contain DNA from other hotspots, indicating that double cutting at distant sites creates substrates for insertional mutagenesis. End joining at double cuts can also yield tandem duplications or extrachromosomal circles. Our findings highlight the importance of DSB regulation and reveal a previously hidden potential for meiotic mutagenesis that is likely to affect human health and genome evolution.
    Keywords DNA ; chromatids ; evolution ; genome ; homologous recombination ; human health ; insertional mutagenesis ; meiosis ; mice
    Language English
    Dates of publication 2021-1124
    Size p. 5970-5984.e18.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.10.025
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  2. Article ; Online: De novo deletions and duplications at recombination hotspots in mouse germlines.

    Lukaszewicz, Agnieszka / Lange, Julian / Keeney, Scott / Jasin, Maria

    Cell

    2021  Volume 184, Issue 24, Page(s) 5970–5984.e18

    Abstract: Numerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here, we uncover a distinct type of mutational event in which deletions form via joining of ends from two ... ...

    Abstract Numerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here, we uncover a distinct type of mutational event in which deletions form via joining of ends from two closely spaced DSBs (double cuts) within a single hotspot or at adjacent hotspots on the same or different chromatids. Deletions occur in normal meiosis but are much more frequent when DSB formation is dysregulated in the absence of the ATM kinase. Events between chromosome homologs point to multi-chromatid damage and aborted gap repair. Some deletions contain DNA from other hotspots, indicating that double cutting at distant sites creates substrates for insertional mutagenesis. End joining at double cuts can also yield tandem duplications or extrachromosomal circles. Our findings highlight the importance of DSB regulation and reveal a previously hidden potential for meiotic mutagenesis that is likely to affect human health and genome evolution.
    MeSH term(s) Animals ; Ataxia Telangiectasia Mutated Proteins/deficiency ; Ataxia Telangiectasia Mutated Proteins/metabolism ; Base Sequence ; Chromatids/metabolism ; Chromosomes, Mammalian/genetics ; Crosses, Genetic ; DNA Breaks, Double-Stranded ; DNA, Circular/genetics ; Female ; Gene Deletion ; Gene Duplication ; Genome ; Germ Cells/metabolism ; Haplotypes/genetics ; Homologous Recombination/genetics ; Male ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mutagenesis, Insertional/genetics ; Mutation/genetics ; Recombination, Genetic/genetics ; Mice
    Chemical Substances DNA, Circular ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1)
    Language English
    Publishing date 2021-11-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.10.025
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  3. Article ; Online: Control of meiotic double-strand-break formation by ATM: local and global views.

    Lukaszewicz, Agnieszka / Lange, Julian / Keeney, Scott / Jasin, Maria

    Cell cycle (Georgetown, Tex.)

    2018  Volume 17, Issue 10, Page(s) 1155–1172

    Abstract: DNA double-strand breaks (DSBs) generated by the SPO11 protein initiate meiotic recombination, an essential process for successful chromosome segregation during gametogenesis. The activity of SPO11 is controlled by multiple factors and regulatory ... ...

    Abstract DNA double-strand breaks (DSBs) generated by the SPO11 protein initiate meiotic recombination, an essential process for successful chromosome segregation during gametogenesis. The activity of SPO11 is controlled by multiple factors and regulatory mechanisms, such that the number of DSBs is limited and DSBs form at distinct positions in the genome and at the right time. Loss of this control can affect genome integrity or cause meiotic arrest by mechanisms that are not fully understood. Here we focus on the DSB-responsive kinase ATM and its functions in regulating meiotic DSB numbers and distribution. We review the recently discovered roles of ATM in this context, discuss their evolutionary conservation, and examine future research perspectives.
    MeSH term(s) Animals ; Ataxia Telangiectasia Mutated Proteins/metabolism ; DNA Breaks, Double-Stranded ; Humans ; Meiosis ; Models, Biological
    Chemical Substances Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1)
    Language English
    Publishing date 2018-07-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.1080/15384101.2018.1464847
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  4. Article ; Online: Exo1 and Mre11 execute meiotic DSB end resection in the protist Tetrahymena.

    Lukaszewicz, Agnieszka / Shodhan, Anura / Loidl, Josef

    DNA repair

    2015  Volume 35, Page(s) 137–143

    Abstract: The resection of 5'-DNA ends at a double-strand break (DSB) is an essential step in recombinational repair, as it exposes 3' single-stranded DNA (ssDNA) tails for interaction with a repair template. In mitosis, Exo1 and Sgs1 have a conserved function in ... ...

    Abstract The resection of 5'-DNA ends at a double-strand break (DSB) is an essential step in recombinational repair, as it exposes 3' single-stranded DNA (ssDNA) tails for interaction with a repair template. In mitosis, Exo1 and Sgs1 have a conserved function in the formation of long ssDNA tails, whereas this step in the processing of programmed meiotic DSBs is less well-characterized across model organisms. In budding yeast, which has been most intensely studied in this respect, Exo1 is a major meiotic nuclease. In addition, it exerts a nuclease-independent function later in meiosis in the conversion of DNA joint molecules into ZMM-dependent crossovers. In order to gain insight into the diverse meiotic roles of Exo1, we investigated the effect of Exo1 deletion in the ciliated protist Tetrahymena. We found that Exo1 together with Mre11, but without the help of Sgs1, promotes meiotic DSB end resection. Resection is completely eliminated only if both Mre11 and Exo1 are missing. This is consistent with the yeast model where Mre11 promotes resection in the 3'-5' direction and Exo1 in the opposite 5'-3' direction. However, while the endonuclease activity of Mre11 is essential to create an entry site for exonucleases and hence to start resection in budding yeast, Tetrahymena Exo1 is able to create single-stranded DNA in the absence of Mre11. Excluding a possible contribution of the Mre11 cofactor Sae2 (Com1) as an autonomous endonuclease, we conclude that there exists another unknown nuclease that initiates DSB processing in Tetrahymena. Consistent with the absence of the ZMM crossover pathway in Tetrahymena, crossover formation is independent of Exo1.
    MeSH term(s) DNA Breaks, Double-Stranded ; DNA, Single-Stranded/metabolism ; Endonucleases/chemistry ; Endonucleases/metabolism ; Exodeoxyribonucleases/genetics ; Exodeoxyribonucleases/metabolism ; Gene Knockout Techniques ; Meiosis ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Recombinational DNA Repair ; Tetrahymena thermophila/enzymology ; Tetrahymena thermophila/genetics
    Chemical Substances DNA, Single-Stranded ; Protozoan Proteins ; Endonucleases (EC 3.1.-) ; Exodeoxyribonucleases (EC 3.1.-) ; exodeoxyribonuclease I (EC 3.1.11.1)
    Language English
    Publishing date 2015-09-26
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2071608-4
    ISSN 1568-7856 ; 1568-7864
    ISSN (online) 1568-7856
    ISSN 1568-7864
    DOI 10.1016/j.dnarep.2015.08.005
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  5. Article ; Online: Msh4 and Msh5 function in SC-independent chiasma formation during the streamlined meiosis of Tetrahymena.

    Shodhan, Anura / Lukaszewicz, Agnieszka / Novatchkova, Maria / Loidl, Josef

    Genetics

    2014  Volume 198, Issue 3, Page(s) 983–993

    Abstract: ZMM proteins have been defined in budding yeast as factors that are collectively involved in the formation of interfering crossovers (COs) and synaptonemal complexes (SCs), and they are a hallmark of the predominant meiotic recombination pathway of most ... ...

    Abstract ZMM proteins have been defined in budding yeast as factors that are collectively involved in the formation of interfering crossovers (COs) and synaptonemal complexes (SCs), and they are a hallmark of the predominant meiotic recombination pathway of most organisms. In addition to this so-called class I CO pathway, a minority of crossovers are formed by a class II pathway, which involves the Mus81-Mms4 endonuclease complex. This is the only CO pathway in the SC-less meiosis of the fission yeast. ZMM proteins (including SC components) were always found to be co-occurring and hence have been regarded as functionally linked. Like the fission yeast, the protist Tetrahymena thermophila does not possess a SC, and its COs are dependent on Mus81-Mms4. Here we show that the ZMM proteins Msh4 and Msh5 are required for normal chiasma formation, and we propose that they have a pro-CO function outside a canonical class I pathway in Tetrahymena. Thus, the two-pathway model is not tenable as a general rule.
    MeSH term(s) Crossing Over, Genetic ; DNA Breaks, Double-Stranded ; DNA, Protozoan/metabolism ; Gene Knockout Techniques ; Meiosis ; Mutation/genetics ; Phylogeny ; Protozoan Proteins/metabolism ; Sequence Homology, Amino Acid ; Synaptonemal Complex/metabolism ; Tetrahymena/cytology ; Tetrahymena/metabolism
    Chemical Substances DNA, Protozoan ; Protozoan Proteins
    Language English
    Publishing date 2014-09-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2167-2
    ISSN 1943-2631 ; 0016-6731
    ISSN (online) 1943-2631
    ISSN 0016-6731
    DOI 10.1534/genetics.114.169698
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  6. Article ; Online: Mus81 nuclease and Sgs1 helicase are essential for meiotic recombination in a protist lacking a synaptonemal complex.

    Lukaszewicz, Agnieszka / Howard-Till, Rachel A / Loidl, Josef

    Nucleic acids research

    2013  Volume 41, Issue 20, Page(s) 9296–9309

    Abstract: Mus81 resolvase and Sgs1 helicase have well-established roles in mitotic DNA repair. Moreover, Mus81 is part of a minor crossover (CO) pathway in the meiosis of budding yeast, plants and vertebrates. The major pathway depends on meiosis-specific ... ...

    Abstract Mus81 resolvase and Sgs1 helicase have well-established roles in mitotic DNA repair. Moreover, Mus81 is part of a minor crossover (CO) pathway in the meiosis of budding yeast, plants and vertebrates. The major pathway depends on meiosis-specific synaptonemal complex (SC) formation, ZMM proteins and the MutLγ complex for CO-directed resolution of joint molecule (JM)-recombination intermediates. Sgs1 has also been implicated in this pathway, although it may mainly promote the non-CO outcome of meiotic repair. We show in Tetrahymena, that homologous chromosomes fail to separate and JMs accumulate in the absence of Mus81 or Sgs1, whereas deletion of the MutLγ-component Mlh1 does not affect meiotic divisions. Thus, our results are consistent with Mus81 being part of an essential, if not the predominant, CO pathway in Tetrahymena. Sgs1 may exert functions similar to those in other eukaryotes. However, we propose an additional role in supporting homologous CO formation by promoting homologous over intersister interactions. Tetrahymena shares the predominance of the Mus81 CO pathway with the fission yeast. We propose that in these two organisms, which independently lost the SC during evolution, the basal set of mitotic repair proteins is sufficient for executing meiotic recombination.
    MeSH term(s) Cell Nucleus/enzymology ; Chromatids ; Chromosome Segregation ; DNA/chemistry ; DNA/metabolism ; DNA Breaks, Double-Stranded ; Endodeoxyribonucleases/metabolism ; Endodeoxyribonucleases/physiology ; Escherichia coli Proteins/metabolism ; Meiosis/genetics ; Mutation ; RNA Interference ; RecQ Helicases/analysis ; RecQ Helicases/antagonists & inhibitors ; RecQ Helicases/physiology ; Recombinases/analysis ; Recombinases/antagonists & inhibitors ; Recombinases/physiology ; Recombination, Genetic ; Synaptonemal Complex ; Tetrahymena thermophila/enzymology ; Tetrahymena thermophila/genetics
    Chemical Substances Escherichia coli Proteins ; Recombinases ; ruvC protein, E coli ; DNA (9007-49-2) ; Endodeoxyribonucleases (EC 3.1.-) ; RecQ Helicases (EC 3.6.4.12)
    Language English
    Publishing date 2013-08-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkt703
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  7. Article ; Online: The recombinases Rad51 and Dmc1 play distinct roles in DNA break repair and recombination partner choice in the meiosis of Tetrahymena.

    Howard-Till, Rachel A / Lukaszewicz, Agnieszka / Loidl, Josef

    PLoS genetics

    2011  Volume 7, Issue 3, Page(s) e1001359

    Abstract: Repair of programmed DNA double-strand breaks (DSBs) by meiotic recombination relies on the generation of flanking 3' single-stranded DNA overhangs and their interaction with a homologous double-stranded DNA template. In various common model organisms, ... ...

    Abstract Repair of programmed DNA double-strand breaks (DSBs) by meiotic recombination relies on the generation of flanking 3' single-stranded DNA overhangs and their interaction with a homologous double-stranded DNA template. In various common model organisms, the ubiquitous strand exchange protein Rad51 and its meiosis-specific homologue Dmc1 have been implicated in the joint promotion of DNA-strand exchange at meiotic recombination sites. However, the division of labor between these two recombinases is still a puzzle. Using RNAi and gene-disruption experiments, we have studied their roles in meiotic recombination and chromosome pairing in the ciliated protist Tetrahymena as an evolutionarily distant meiotic model. Cytological and electrophoresis-based assays for DSBs revealed that, without Rad51p, DSBs were not repaired. However, in the absence of Dmc1p, efficient Rad51p-dependent repair took place, but crossing over was suppressed. Immunostaining and protein tagging demonstrated that only Dmc1p formed strong DSB-dependent foci on meiotic chromatin, whereas the distribution of Rad51p was diffuse within nuclei. This suggests that meiotic nucleoprotein filaments consist primarily of Dmc1p. Moreover, a proximity ligation assay confirmed that little if any Rad51p forms mixed nucleoprotein filaments with Dmc1p. Dmc1p focus formation was independent of the presence of Rad51p. The absence of Dmc1p did not result in compensatory assembly of Rad51p repair foci, and even artificial DNA damage by UV failed to induce Rad51p foci in meiotic nuclei, while it did so in somatic nuclei within one and the same cell. The observed interhomologue repair deficit in dmc1Δ meiosis is consistent with a requirement for Dmc1p in promoting the homologue as the preferred recombination partner. We propose that relatively short and/or transient Rad51p nucleoprotein filaments are sufficient for intrachromosomal recombination, whereas long nucleoprotein filaments consisting primarily of Dmc1p are required for interhomolog recombination.
    MeSH term(s) Cell Cycle Proteins/genetics ; Cell Cycle Proteins/physiology ; Crossing Over, Genetic ; DNA Breaks, Double-Stranded ; DNA Repair/genetics ; DNA, Single-Stranded/genetics ; Meiosis/genetics ; Rad51 Recombinase/genetics ; Rad51 Recombinase/physiology ; Recombination, Genetic ; Tetrahymena/cytology ; Tetrahymena/enzymology ; Tetrahymena/genetics
    Chemical Substances Cell Cycle Proteins ; DNA, Single-Stranded ; Rad51 Recombinase (EC 2.7.7.-)
    Language English
    Publishing date 2011-03-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1001359
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  8. Article ; Online: A single cohesin complex performs mitotic and meiotic functions in the protist tetrahymena.

    Howard-Till, Rachel A / Lukaszewicz, Agnieszka / Novatchkova, Maria / Loidl, Josef

    PLoS genetics

    2013  Volume 9, Issue 3, Page(s) e1003418

    Abstract: The cohesion of sister chromatids in the interval between chromosome replication and anaphase is important for preventing the precocious separation, and hence nondisjunction, of chromatids. Cohesion is accomplished by a ring-shaped protein complex, ... ...

    Abstract The cohesion of sister chromatids in the interval between chromosome replication and anaphase is important for preventing the precocious separation, and hence nondisjunction, of chromatids. Cohesion is accomplished by a ring-shaped protein complex, cohesin; and its release at anaphase occurs when separase cleaves the complex's α-kleisin subunit. Cohesin has additional roles in facilitating DNA damage repair from the sister chromatid and in regulating gene expression. We tested the universality of the present model of cohesion by studying cohesin in the evolutionarily distant protist Tetrahymena thermophila. Localization of tagged cohesin components Smc1p and Rec8p (the α-kleisin) showed that cohesin is abundant in mitotic and meiotic nuclei. RNAi knockdown experiments demonstrated that cohesin is crucial for normal chromosome segregation and meiotic DSB repair. Unexpectedly, cohesin does not detach from chromosome arms in anaphase, yet chromosome segregation depends on the activity of separase (Esp1p). When Esp1p is depleted by RNAi, chromosomes become polytenic as they undergo multiple rounds of replication, but fail to separate. The cohesion of such bundles of numerous chromatids suggests that chromatids may be connected by factors in addition to topological linkage by cohesin rings. Although cohesin is not detected in transcriptionally active somatic nuclei, its loss causes a slight defect in their amitotic division. Notably, Tetrahymena uses a single version of α-kleisin for both mitosis and meiosis. Therefore, we propose that the differentiation of mitotic and meiotic cohesins found in most other model systems is not due to the need of a specialized meiotic cohesin, but due to additional roles of mitotic cohesin.
    MeSH term(s) Amino Acid Sequence ; Animals ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosome Segregation/genetics ; DNA Damage ; DNA Repair/genetics ; Endopeptidases/metabolism ; Meiosis/genetics ; Mitosis/genetics ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Separase ; Tetrahymena/cytology ; Tetrahymena/genetics ; Cohesins
    Chemical Substances Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; Multiprotein Complexes ; structural maintenance of chromosome protein 1 ; Endopeptidases (EC 3.4.-) ; Separase (EC 3.4.22.49)
    Language English
    Publishing date 2013-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1003418
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  9. Article ; Online: The Tetrahymena meiotic chromosome bouquet is organized by centromeres and promotes interhomolog recombination.

    Loidl, Josef / Lukaszewicz, Agnieszka / Howard-Till, Rachel A / Koestler, Tina

    Journal of cell science

    2012  Volume 125, Issue Pt 23, Page(s) 5873–5880

    Abstract: In order to form crossovers and to undergo reductional segregation during meiosis, homologous chromosomes must pair. In Tetrahymena, meiotic prophase nuclei elongate immensely, and, within the elongated nucleus, chromosomes are arranged with telomeres ... ...

    Abstract In order to form crossovers and to undergo reductional segregation during meiosis, homologous chromosomes must pair. In Tetrahymena, meiotic prophase nuclei elongate immensely, and, within the elongated nucleus, chromosomes are arranged with telomeres assembled at one pole and centromeres at the opposite pole. This organisation is an exaggerated form of the bouquet, a meiotic chromosome arrangement that is widely conserved among eukaryotes. We show that centromere function is crucial for the formation of Tetrahymena's stretched bouquet and, thereby, for homologue pairing. This finding adds to previous reports of the importance of centromeres in chromosome pairing in budding yeast and in Drosophila. Tetrahymena's bouquet is an ataxia telangiectasia- and RAD3-related (ATR)-dependent meiotic DNA damage response that is triggered by meiotic DNA double-strand breaks (DSBs), suggesting that the bouquet is needed for DSB repair. However, in the present study we show that although homologous pairing is impeded in the absence of the bouquet, DSB repair takes place nevertheless. Moreover, recombinational DSB repair, as monitored by bromodeoxyuridine incorporation, takes place only after exit from the bouquet stage. Therefore, we conclude that the bouquet is not required for DSB repair per se, but may be necessary for the alignment of homologous loci in order to promote homologous crossovers over alternative repair pathways.
    MeSH term(s) Centromere/genetics ; Chromosome Pairing/genetics ; Chromosomes/genetics ; Meiosis/genetics ; Recombination, Genetic/genetics ; Tetrahymena/genetics
    Language English
    Publishing date 2012-09-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.112664
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  10. Article: MRE11 and COM1/SAE2 are required for double-strand break repair and efficient chromosome pairing during meiosis of the protist Tetrahymena

    Lukaszewicz, Agnieszka / Howard-Till, Rachel A / Novatchkova, Maria / Mochizuki, Kazufumi / Loidl, Josef

    Chromosoma. 2010 Oct., v. 119, no. 5

    2010  

    Abstract: Programmed DNA double-strand breaks (DSBs) are generated during meiosis to initiate homologous recombination. Various aspects of DSB formation, signaling, and repair are accomplished or governed by Mre11, a component of the MRN/MRX complex, partially in ... ...

    Abstract Programmed DNA double-strand breaks (DSBs) are generated during meiosis to initiate homologous recombination. Various aspects of DSB formation, signaling, and repair are accomplished or governed by Mre11, a component of the MRN/MRX complex, partially in cooperation with Com1/Sae2/CtIP. We used Tetrahymena to study evolutionarily conserved and changed functions of Mre11 and Com1. There is a difference between organisms with respect to the dependency of meiotic DSB formation on Mre11. By cytology and an electrophoresis-based assay for DSBs, we found that in Tetrahymena Mre11p is not required for the formation and ATR-dependent signaling of DSBs. Its dispensability is also reflected by wild-type-like DSB-dependent reorganization of the meiotic nucleus and by the phosphorylation of H2A.X in mre11∆ mutant. However, mre11∆ and com1∆ mutants are unable to repair DSBs, and chromosome pairing is reduced. It is concluded that, while MRE11 has no universal role in DNA damage signaling, its requirement for DSB repair is conserved between evolutionarily distant organisms. Moreover, reduced chromosome pairing in repair-deficient mutants reveals the existence of two complementing pairing processes, one by the rough parallel arrangement of chromosomes imposed by the tubular shape of the meiotic nucleus and the other by repair-dependent precise sequence matching.
    Keywords DNA damage ; Tetrahymena ; chromosome pairing ; chromosomes ; homologous recombination ; meiosis ; mutants ; phosphorylation
    Language English
    Dates of publication 2010-10
    Size p. 505-518.
    Publisher Springer-Verlag
    Publishing place Berlin/Heidelberg
    Document type Article
    ZDB-ID 203083-4
    ISSN 1432-0886 ; 0009-5915
    ISSN (online) 1432-0886
    ISSN 0009-5915
    DOI 10.1007/s00412-010-0274-9
    Database NAL-Catalogue (AGRICOLA)

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