Diverse roles for CDK‐associated activity during spermatogenesis

Palmer, Nathan; Talib, S. Zakiah A.; Kaldis, Philipp

doi:10.1002/1873-3468.13627

Cited by 24 publications

(20 citation statements)

References 254 publications

(325 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CDK2 is a multifunctional kinase that is recognized to play multiple roles during germ cell development. These include regulating cell fate in spermatogonial stem cells [ 17 ], regulation of transcription in spermatocytes [ 18 ], and promoting homolog synapsis during meiotic prophase I ([ 10 ]; for reviews, also see [ 19 – 22 ]). During zygonema of meiotic prophase, CDK2 and its noncanonical activating partner Speedy A (see below) interact to promote stable interactions between telomeres and the inner nuclear envelope.…”

Section: Introductionmentioning

confidence: 99%

“…During zygonema of meiotic prophase, CDK2 and its noncanonical activating partner Speedy A (see below) interact to promote stable interactions between telomeres and the inner nuclear envelope. This action is essential for the DSB-stimulated homology search process needed for pairing of homologous chromosomes ([ 23 – 25 ]; reviewed in [ 19 ]; see also [ 26 ]). Consequentially, Cdk2 −/− and Speedy A −/− meiocytes display extensive nonhomologous synapsis and arrest at an identical pachytene-like stage [ 10 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel function for CDK2 activity at meiotic crossover sites

et al. 2020

Self Cite

View full text Add to dashboard Cite

Genetic diversity in offspring is induced by meiotic recombination, which is initiated between homologs at >200 sites originating from meiotic double-strand breaks (DSBs). Of this initial pool, only 1–2 DSBs per homolog pair will be designated to form meiotic crossovers (COs), where reciprocal genetic exchange occurs between parental chromosomes. Cyclin-dependent kinase 2 (CDK2) is known to localize to so-called “late recombination nodules” (LRNs) marking incipient CO sites. However, the role of CDK2 kinase activity in the process of CO formation remains uncertain. Here, we describe the phenotype of 2 Cdk2 point mutants with elevated or decreased activity, respectively. Elevated CDK2 activity was associated with increased numbers of LRN-associated proteins, including CDK2 itself and the MutL homolog 1 (MLH1) component of the MutLγ complex, but did not lead to increased numbers of COs. In contrast, reduced CDK2 activity leads to the complete absence of CO formation during meiotic prophase I. Our data suggest an important role for CDK2 in regulating MLH1 focus numbers and that the activity of this kinase is a key regulatory factor in the formation of meiotic COs.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel function for CDK2 activity at meiotic crossover sites

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The kinase activity of CDK2 is important for meiosis and spermatogenesis (Liu et al, 2014;Wang et al, 2014;Chauhan et al, 2016;Palmer et al, 2019). It has been reported that CDK2 phosphorylates SUN1 (Viera et al, 2015;Mikolcevic et al, 2016), but the function of SUN1 phosphorylation by CDK2 is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…CDK2 and its activators, SPDYA and Cyclin E, are required for the bouquet formation (Palmer et al, 2019). In the Cdk2, Spdya, and Cyclin E knockout mice, telomeres dissociate from the NE, indicating that the LINC-linker-shelterin connection is broken down, but where the disconnection occurs is unknown (Viera et al, 2015;Manterola et al, 2016;Tu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Tethering of Telomeres to the Nuclear Envelope Is Mediated by SUN1-MAJIN and Possibly Promoted by SPDYA-CDK2 During Meiosis

Wang

Zhou

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

During meiosis, telomeres attach to the nuclear envelope (NE) to promote homologous chromosome moving, pairing, synapsis, and recombination. The telomere-NE attachment is mediated by SUN1, TERB1-TERB2-MAJIN (TTM complex), and TRF1. The interaction of the TTM complex with shelterin is mediated by TERB1 and TRF1, but how SUN1 interacts with the TTM complex is not yet fully understood. In this study, we found that SUN1 not only interacted with TERB1 but also interacted with MAJIN, and the interaction of SUN1 with MAJIN is stronger than TERB1. We also found that SUN1 interacted with SPDYA, an activator of CDK2. The binding sites of MAJIN and SPDYA at SUN1 were mapped, and both MAJIN and SPDYA bound to the N-terminal domain of SUN1 and the two binding sites were close to each other. Furthermore, SPDYA bound to SUN1 via the Ringo domain and recruited CDK2 to SUN1. Then, we found that the interaction of SUN1 with MAJIN was decreased by the CDK2 inhibitors. Taken together, our results provide the possible mechanism of SUN1, MAJIN, and SPDYA-CDK2 in promoting the telomere-NE attachment during meiosis.

show abstract

“…In this mutant, unresolved class II recombination intermediates persist, leading to the formation of chromosome entanglements at metaphase I (Crismani et al, 2012). MUS81 has a well-described role in the resolution of Holliday junctions (Osman et al, 2003) and there is also support for CDKs having a role in CO maturation (Palmer et al, 2019).…”

Section: The Localisation Of Class I Co Markers Is Restored In a Doubmentioning

confidence: 98%

CDKG1 Is Required for Meiotic and Somatic Recombination Intermediate Processing in Arabidopsis

et al. 2020

View full text Add to dashboard Cite

Short title: The role of CDKG1 in recombinationOne-sentence summary: The cyclin-dependent kinase CDKG1 stabilises recombination intermediates during male meiosis and DNA damage-induced somatic homologous recombination. ABSTRACTThe Arabidopsis thaliana cyclin-dependent kinase G1 (CDKG1) is necessary for recombination and synapsis during male meiosis at high ambient temperature. In the cdkg1-1 mutant, synapsis is impaired and there is a dramatic reduction in the number of class I crossovers resulting in univalents at metaphase I and pollen sterility. Here we demonstrate that CDKG1 is necessary for the processing of recombination intermediates in the canonical ZMM recombination pathway and that loss of CDKG1 results in increased class II crossovers. While synapsis and events associated with class I crossovers are severely compromised in a cdkg1-1 mutant, they can be restored by increasing the number of recombination intermediates in the double cdkg1-1 fancm-1 mutant. Despite this, recombination intermediates are not correctly resolved, leading to the formation of chromosome aggregates at metaphase I. Our results show that CDKG1 acts early in the recombination process and is necessary to stabilize recombination intermediates. Finally, we show that the effect on recombination is not restricted to meiosis and that CDKG1 is also required for normal levels of DNA damage-induced homologous recombination in somatic tissues. . Both ATM and ATR promote the efficient and accurate processing of programmed meiotic double-strand breaks. The Plant Journal 55, 629-638. Dangel, N.J., Knoll, A., and Puchta, H. (2014). MHF1 plays Fanconi anaemia complementation group M protein (FANCM)-dependent and FANCM-independent roles in DNA repair and homologous recombination in plants.

show abstract

Diverse roles for CDK‐associated activity during spermatogenesis

Cited by 24 publications

References 254 publications

A novel function for CDK2 activity at meiotic crossover sites

A novel function for CDK2 activity at meiotic crossover sites

Tethering of Telomeres to the Nuclear Envelope Is Mediated by SUN1-MAJIN and Possibly Promoted by SPDYA-CDK2 During Meiosis

CDKG1 Is Required for Meiotic and Somatic Recombination Intermediate Processing in Arabidopsis

Contact Info

Product

Resources

About