scholarly journals RAD21L, a novel cohesin subunit implicated in linking homologous chromosomes in mammalian meiosis

2011 ◽  
Vol 192 (2) ◽  
pp. 263-276 ◽  
Author(s):  
Jibak Lee ◽  
Tatsuya Hirano
Keyword(s):  
Molecular Markers ◽  
Sister Chromatid ◽  
Protein Complexes ◽  
Strand Break ◽  
S Phase ◽  
Homologous Chromosomes ◽  
Dna Double Strand Break ◽  
Chromatid Cohesion ◽  
Cohesin Subunit ◽  
Mitosis And Meiosis

Cohesins are multi-subunit protein complexes that regulate sister chromatid cohesion during mitosis and meiosis. Here we identified a novel kleisin subunit of cohesins, RAD21L, which is conserved among vertebrates. In mice, RAD21L is expressed exclusively in early meiosis: it apparently replaces RAD21 in premeiotic S phase, becomes detectable on the axial elements in leptotene, and stays on the axial/lateral elements until mid pachytene. RAD21L then disappears, and is replaced with RAD21. This behavior of RAD21L is unique and distinct from that of REC8, another meiosis-specific kleisin subunit. Remarkably, the disappearance of RAD21L at mid pachytene correlates with the completion of DNA double-strand break repair and the formation of crossovers as judged by colabeling with molecular markers, γ-H2AX, MSH4, and MLH1. RAD21L associates with SMC3, STAG3, and either SMC1α or SMC1β. Our results suggest that cohesin complexes containing RAD21L may be involved in synapsis initiation and crossover recombination between homologous chromosomes.

scholarly journals Recruitment of Rec8, Pds5 and Rad61/Wapl to meiotic homolog pairing, recombination, axis formation and S-phase

2019 ◽  
Author(s):  
Soogil Hong ◽  
Jeong H Joo ◽  
Hyeseon Yun ◽  
Nancy Kleckner ◽  
Keun P Kim
Keyword(s):  
Sister Chromatid ◽  
Strand Break ◽  
S Phase ◽  
Axis Formation ◽  
Unique Role ◽  
Homolog Pairing ◽  
Chromatid Cohesion ◽  
Phase Progression ◽  
Axis Length

Abstract We have explored the meiotic roles of cohesin modulators Pds5 and Rad61/Wapl, in relation to one another, and to meiotic kleisin Rec8, for homolog pairing, all physically definable steps of recombination, prophase axis length and S-phase progression, in budding yeast. We show that Pds5 promotes early steps of recombination and thus homolog pairing, and also modulates axis length, with both effects independent of a sister chromatid. [Pds5+Rec8] promotes double-strand break formation, maintains homolog bias for crossover formation and promotes S-phase progression. Oppositely, the unique role of Rad61/Wapl is to promote non-crossover recombination by releasing [Pds5+Rec8]. For this effect, Rad61/Wapl probably acts to maintain homolog bias by preventing channeling into sister interactions. Mysteriously, each analyzed molecule has one role that involves neither of the other two. Overall, the presented findings suggest that Pds5’s role in maintenance of sister chromatid cohesion during the mitotic prophase-analogous stage of G2/M is repurposed during meiosis prophase to promote interactions between homologs.

scholarly journals Repair Kinetics of Genomic Interstrand DNA Cross-Links: Evidence for DNA Double-Strand Break-Dependent Activation of the Fanconi Anemia/BRCA Pathway

2004 ◽  
Vol 24 (1) ◽  
pp. 123-134 ◽  
Author(s):  
Andreas Rothfuss ◽  
Markus Grompe
Keyword(s):  
Fanconi Anemia ◽  
Strand Break ◽  
S Phase ◽  
Dna Double Strand Breaks ◽  
Subsequent Formation ◽  
Strand Breaks ◽  
Dna Double Strand Break ◽  
Cross Links ◽  
Kinetics Of

ABSTRACT The detailed mechanisms of DNA interstrand cross-link (ICL) repair and the involvement of the Fanconi anemia (FA)/BRCA pathway in this process are not known. Present models suggest that recognition and repair of ICL in human cells occur primarily during the S phase. Here we provide evidence for a refined model in which ICLs are recognized and are rapidly incised by ERCC1/XPF independent of DNA replication. However, the incised ICLs are then processed further and DNA double-strand breaks (DSB) form exclusively in the S phase. FA cells are fully proficient in the sensing and incision of ICL as well as in the subsequent formation of DSB, suggesting a role of the FA/BRCA pathway downstream in ICL repair. In fact, activation of FANCD2 occurs slowly after ICL treatment and correlates with the appearance of DSB in the S phase. In contrast, activation is rapid after ionizing radiation, indicating that the FA/BRCA pathway is specifically activated upon DSB formation. Furthermore, the formation of FANCD2 foci is restricted to a subpopulation of cells, which can be labeled by bromodeoxyuridine incorporation. We therefore conclude that the FA/BRCA pathway, while being dispensable for the early events in ICL repair, is activated in S-phase cells after DSB have formed.

scholarly journals PCNA Controls Establishment of Sister Chromatid Cohesion during S Phase

2006 ◽  
Vol 23 (5) ◽  
pp. 723-732 ◽  
Author(s):  
George-Lucian Moldovan ◽  
Boris Pfander ◽  
Stefan Jentsch
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Chromatid Cohesion

scholarly journals Hst3 Is Regulated by Mec1-dependent Proteolysis and Controls the S Phase Checkpoint and Sister Chromatid Cohesion by Deacetylating Histone H3 at Lysine 56

2007 ◽  
Vol 282 (52) ◽  
pp. 37805-37814 ◽  
Author(s):  
Safia Thaminy ◽  
Benjamin Newcomb ◽  
Jessica Kim ◽  
Tonibelle Gatbonton ◽  
Eric Foss ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Histone H3 ◽  
Sister Chromatid Cohesion ◽  
S Phase ◽  
Chromatid Cohesion ◽  
S Phase Checkpoint

scholarly journals Trex2 Enables Spontaneous Sister Chromatid Exchanges Without Facilitating DNA Double-Strand Break Repair

Genetics ◽  
2011 ◽  
Vol 188 (4) ◽  
pp. 787-797 ◽  
Author(s):  
Lavinia C. Dumitrache ◽  
Lingchuan Hu ◽  
Mi Young Son ◽  
Han Li ◽  
Austin Wesevich ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Strand Break ◽  
Double Strand Break ◽  
Sister Chromatid Exchanges ◽  
Double Strand Break Repair ◽  
Dna Double Strand Break ◽  
Break Repair ◽  
Chromatid Exchanges

scholarly journals Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1β and SMC3

2003 ◽  
Vol 160 (5) ◽  
pp. 657-670 ◽  
Author(s):  
Maureen Eijpe ◽  
Hildo Offenberg ◽  
Rolf Jessberger ◽  
Ekaterina Revenkova ◽  
Christa Heyting
Keyword(s):  
Synaptonemal Complex ◽  
Sister Chromatid ◽  
Meiotic Prophase ◽  
S Phase ◽  
Synaptonemal Complexes ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Axial Element ◽  
Striking Contrast ◽  
Metaphase I

In meiotic prophase, the sister chromatids of each chromosome develop a common axial element (AE) that is integrated into the synaptonemal complex (SC). We analyzed the incorporation of sister chromatid cohesion proteins (cohesins) and other AE components into AEs. Meiotic cohesin REC8 appeared shortly before premeiotic S phase in the nucleus and formed AE-like structures (REC8-AEs) from premeiotic S phase on. Subsequently, meiotic cohesin SMC1β, cohesin SMC3, and AE proteins SCP2 and SCP3 formed dots along REC8-AEs, which extended and fused until they lined REC8-AEs along their length. In metaphase I, SMC1β, SMC3, SCP2, and SCP3 disappeared from the chromosome arms and accumulated around the centromeres, where they stayed until anaphase II. In striking contrast, REC8 persisted along the chromosome arms until anaphase I and near the centromeres until anaphase II. We propose that REC8 provides a basis for AE formation and that the first steps in AE assembly do not require SMC1β, SMC3, SCP2, and SCP3. Furthermore, SMC1β, SMC3, SCP2, and SCP3 cannot provide arm cohesion during metaphase I. We propose that REC8 then provides cohesion. RAD51 and/or DMC1 coimmunoprecipitates with REC8, suggesting that REC8 may also provide a basis for assembly of recombination complexes.

scholarly journals The Multiple Roles of Cohesin in Meiotic Chromosome Morphogenesis and Pairing

2009 ◽  
Vol 20 (3) ◽  
pp. 1030-1047 ◽  
Author(s):  
Gloria A. Brar ◽  
Andreas Hochwagen ◽  
Ly-sha S. Ee ◽  
Angelika Amon
Keyword(s):  
Sister Chromatid ◽  
Meiotic Prophase ◽  
Meiotic Chromosome ◽  
Sister Chromatid Cohesion ◽  
Multiple Roles ◽  
Axis Formation ◽  
Chromatid Cohesion ◽  
Cohesin Subunit ◽  
Chromosome Axis ◽  
Segregation Of Chromosomes

Sister chromatid cohesion, mediated by cohesin complexes, is laid down during DNA replication and is essential for the accurate segregation of chromosomes. Previous studies indicated that, in addition to their cohesion function, cohesins are essential for completion of recombination, pairing, meiotic chromosome axis formation, and assembly of the synaptonemal complex (SC). Using mutants in the cohesin subunit Rec8, in which phosphorylated residues were mutated to alanines, we show that cohesin phosphorylation is not only important for cohesin removal, but that cohesin's meiotic prophase functions are distinct from each other. We find pairing and SC formation to be dependent on Rec8, but independent of the presence of a sister chromatid and hence sister chromatid cohesion. We identified mutations in REC8 that differentially affect Rec8's cohesion, pairing, recombination, chromosome axis and SC assembly function. These findings define Rec8 as a key determinant of meiotic chromosome morphogenesis and a central player in multiple meiotic events.

scholarly journals Quantitative Cytogenetics Reveals Molecular Stoichiometry and Longitudinal Organization of Meiotic Chromosome Axes and Loops

2019 ◽  
Author(s):  
Alexander Woglar ◽  
Kei Yamaya ◽  
Baptiste Roelens ◽  
Alistair Boettiger ◽  
Simone Köhler ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
De Novo ◽  
Meiotic Chromosome ◽  
S Phase ◽  
C Elegans ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Molecular Bases ◽  
Chromosome Axis ◽  
Specialized Organization

ABSTRACTDuring meiosis, chromosomes adopt a specialized organization involving assembly of a cohesin-based axis along their lengths, with DNA loops emanating from this axis. We applied novel, quantitative and widely applicable cytogenetic strategies to elucidate the molecular bases of this organization using C. elegans. Analyses of WT chromosomes and de novo circular mini-chromosomes revealed that meiosis-specific HORMA-domain proteins assemble into cohorts in defined numbers and co-organize the axis together with two functionally-distinct cohesin complexes (REC-8 and COH-3/4) in defined stoichiometry. We further found that REC-8 cohesins, which load during S phase and mediate sister chromatid cohesion, usually occur as individual complexes, supporting a model wherein sister cohesion is mediated locally by a single cohesin ring. REC-8 complexes are interspersed in an alternating pattern with cohorts of axis-organizing COH-3/4 complexes (averaging three per cohort), which are insufficient to confer cohesion but can bind to individual chromatids, suggesting a mechanism to enable formation of asymmetric sister chromatid loops. Indeed, immuno-FISH assays demonstrate frequent asymmetry in genomic content between the loops formed on sister chromatids. We discuss how features of chromosome axis/loop architecture inferred from our data can help to explain enigmatic, yet essential, aspects of the meiotic program.

scholarly journals ATR is a multifunctional regulator of male mouse meiosis

2017 ◽  
Author(s):  
Alexander Widger ◽  
Shantha K Mahadevaiah ◽  
Julian Lange ◽  
Elias Ellnati ◽  
Jasmin Zohren ◽  
...  
Keyword(s):  
Dna Damage ◽  
Male Mouse ◽  
Germ Line ◽  
Strand Break ◽  
Phosphatidylinositol 3 Kinase ◽  
Homologous Chromosomes ◽  
Dna Double Strand Break ◽  
Surveillance Mechanism ◽  
Chromosome Axis ◽  
Deficient Mice

Meiotic cells undergo genetic exchange between homologous chromosomes through programmed DNA double-strand break (DSB) formation, recombination and synapsis1, 2. In mice, the DNA damage-regulated phosphatidylinositol-3-kinase-like kinase (PIKK) ATM regulates all of these processes3-6. However, the meiotic functions of another major PIKK, ATR, have remained elusive, because germ line-specific depletion of this kinase is challenging. Using an efficient conditional strategy, we uncover roles for ATR in male mouse prophase I progression. Deletion of ATR causes chromosome axis fragmentation and germ cell elimination at mid pachynema. ATR is required for homologous synapsis, in a manner genetically dissociable from DSB formation. In addition, ATR regulates loading of recombinases RAD51 and DMC1 to DSBs and maintenance of recombination foci on synapsed and asynapsed chromosomes. Mid pachytene spermatocyte elimination in ATR deficient mice cannot be rescued by deletion of ATM and the third DNA damage-regulated PIKK, PRKDC, consistent with the existence of a PIKK-independent surveillance mechanism in the mammalian germ line. Our studies identify ATR as a multifunctional regulator of mouse meiosis.

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