NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis

Zhang, Bin; Tang, Zhenghui; Li, Lejun; Lu, Lin-Yu

doi:10.1038/s41418-020-0493-4

Cited by 26 publications

(22 citation statements)

References 72 publications

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“…DSB levels, as inferred from RAD51 foci, were elevated on the sex chromosomes in H2ax-Y142A but not Mdc1 KO spermatocytes ( Abe et al, 2020 ), which may point to a role for this residue in regulating DSB repair on asynaptic chromosomes, presumably by inter-sister repair. Interestingly, recruitment of the FHA domain of NBS1 to XY axes requires protein phosphorylation but not MDC1 ( Zhang et al, 2020 ), and may thus be influenced by these histone marks.…”

Section: Formation Of Nuclear Bodiesmentioning

confidence: 99%

Phospho-Regulation of Meiotic Prophase

Kar

Hochwagen

2021

Front. Cell Dev. Biol.

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Germ cells undergoing meiosis rely on an intricate network of surveillance mechanisms that govern the production of euploid gametes for successful sexual reproduction. These surveillance mechanisms are particularly crucial during meiotic prophase, when cells execute a highly orchestrated program of chromosome morphogenesis and recombination, which must be integrated with the meiotic cell division machinery to ensure the safe execution of meiosis. Dynamic protein phosphorylation, controlled by kinases and phosphatases, has emerged as one of the main signaling routes for providing readout and regulation of chromosomal and cellular behavior throughout meiotic prophase. In this review, we discuss common principles and provide detailed examples of how these phosphorylation events are employed to ensure faithful passage of chromosomes from one generation to the next.

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Section: Formation Of Nuclear Bodiesmentioning

confidence: 99%

Phospho-Regulation of Meiotic Prophase

Kar

Hochwagen

2021

Front. Cell Dev. Biol.

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“…It is possible that nuclear TG2 translocated into cytoplasm after performing its function in DNA damage repair. Moreover, TG2 nuclear translocation was only found in response to DSB, the most severe DNA damage, instead of SSB or DNA crosslink [ 24 ]. This finding indicates some unknown signals relative to DSB may be uniquely induced for active mobilization of TG2 nuclear translocation.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Transglutaminase 2 interacts with topoisomerase II⍺ to promote DNA damage repair in lung cancer cells

Xiao

Cao²,

Chen³

et al. 2021

J Exp Clin Cancer Res

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Background To block repairs of DNA damages, especially the DNA double strand break (DSB) repair, can be used to induce cancer cell death. DSB repair depends on a sequential activation of DNA repair factors that may be potentially targeted for clinical cancer therapy. Up to now, many protein components of DSB repair complex remain unclear or poorly characterized. In this study, we discovered that Transglutaminase 2 (TG2) acted as a new component of DSB repair complex. Methods A bioinformatic analysis was performed to identify DNA damage relative genes from dataset from The Cancer Genome Atlas. Immunofluorescence and confocal microscopy were used to monitor the protein localization and recruitment kinetics. Furthermore, immunoprecipitation and mass spectrometry analysis were performed to determine protein interaction of both full-length and fragments or mutants in distinct domain. In situ lung cancer model was used to study the effects cancer therapy in vivo. Results After DSB induction, cytoplasmic TG2 was extensively mobilized and translocated into nucleus after phosphorylated at T162 site by DNA-PKcs. Nuclear TG2 quickly accumulated at DSB sites and directly interacting with Topoisomerase IIα (TOPOIIα) with its TGase domain to promote DSB repair. TG2 deficient cells lost capacity of DSB repair and become susceptible to ionizing radiation. Specific inhibition of TG2-TOPOIIα interaction by glucosamine also significantly inhibited DSB repair, which increased sensitivity in lung cancer cells and engrafted lung cancers. Conclusions These findings elucidate new mechanism of TG2 in DSB repair trough directly interacting with TOPOIIα, inhibition of which provided potential target for overcoming cancer resistance.

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“…In mice, DSB processing is thought to be similar with a conserved role for MRN/MRX complex. However, EXO1 appears to be redundant with other long range resection mechanisms ( Zhang B. et al, 2020 ; Paiano et al, 2020 ; Yamada et al, 2020 ).…”

Section: End Processing and Assembly Of Ssdna Binding Proteins At The Break Sitementioning

confidence: 99%

High Resolution View on the Regulation of Recombinase Accumulation in Mammalian Meiosis

Mhaskar

Koornneef

Zelensky

et al. 2021

Front. Cell Dev. Biol.

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A distinguishing feature of meiotic DNA double-strand breaks (DSBs), compared to DSBs in somatic cells, is the fact that they are induced in a programmed and specifically orchestrated manner, which includes chromatin remodeling prior to DSB induction. In addition, the meiotic homologous recombination (HR) repair process that follows, is different from HR repair of accidental DSBs in somatic cells. For instance, meiotic HR involves preferred use of the homolog instead of the sister chromatid as a repair template and subsequent formation of crossovers and non-crossovers in a tightly regulated manner. An important outcome of this distinct repair pathway is the pairing of homologous chromosomes. Central to the initial steps in homology recognition during meiotic HR is the cooperation between the strand exchange proteins (recombinases) RAD51 and its meiosis-specific paralog DMC1. Despite our understanding of their enzymatic activity, details on the regulation of their assembly and subsequent molecular organization at meiotic DSBs in mammals have remained largely enigmatic. In this review, we summarize recent mouse data on recombinase regulation via meiosis-specific factors. Also, we reflect on bulk “omics” studies of initial meiotic DSB processing, compare these with studies using super-resolution microscopy in single cells, at single DSB sites, and explore the implications of these findings for our understanding of the molecular mechanisms underlying meiotic HR regulation.

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NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis

Cited by 26 publications

References 72 publications

Phospho-Regulation of Meiotic Prophase

Phospho-Regulation of Meiotic Prophase

Nuclear Transglutaminase 2 interacts with topoisomerase II⍺ to promote DNA damage repair in lung cancer cells

High Resolution View on the Regulation of Recombinase Accumulation in Mammalian Meiosis

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