The MMS22L-TONSL Complex Mediates Recovery from Replication Stress and Homologous Recombination

O’Donnell, Lara; Panier, Stephanie; Wildenhain, Jan; Tkach, Johnny M.; Al-Hakim, Abdallah; Landry, Marie-Claude; Escribano-Díaz, Cristina; Szilard, Rachel K.; Young, Jordan T.F.; Munro, Meagan; Canny, Marella D.; Kolas, Nadine K.; Zhang, Wei; Harding, Shane M.; Ylanko, Jarkko; Mendez, Megan; Mullin, Michael; Sun, Thomas; Habermann, Bianca; Datti, Alessandro; Bristow, Robert G.; Gingras, Anne‐Claude; Tyers, Michael; Brown, Grant W.; Durocher, Daniel

doi:10.1016/j.molcel.2010.10.024

Cited by 109 publications

(133 citation statements)

References 50 publications

(60 reference statements)

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“…Consistent with this possibility, the catalytic subunit of DNA polymerase α in the budding yeast S. cerevisiae has been reported to form a complex with SPT16, a subunit of the FACT chromatin assembly factor (Wittmeyer and Formosa, 1997). Fortunately, many recent reports have characterized diverse epigenetic defects in Arabidopsis and mammals with mutations in various components of the DNA replication machinery (del Olmo et al, 2010;Liu et al, 2010b;O'Donnell et al, 2010;Xia et al, 2006;Yin et al, 2009). Additional studies that investigate the functional and biochemical relationship between ICU2 and these factors will provide further insights into DNA replication-coupled epigenetic inheritance.…”

Section: Roles Of Dna Replication Machinery In Epigenetic Maintenancementioning

confidence: 88%

The catalytic subunit ofArabidopsisDNA polymerase α ensures stable maintenance of histone modification

et al. 2013

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SUMMARYMitotic inheritance of identical cellular memory is crucial for development in multicellular organisms. The cell type-specific epigenetic state should be correctly duplicated upon DNA replication to maintain cellular memory during tissue and organ development. Although a role of DNA replication machinery in maintenance of epigenetic memory has been proposed, technical limitations have prevented characterization of the process in detail. Here, we show that INCURVATA2 (ICU2), the catalytic subunit of DNA polymerase a in Arabidopsis, ensures the stable maintenance of repressive histone modifications. The missense mutant allele icu2-1 caused a defect in the mitotic maintenance of vernalization memory. Although neither the recruitment of CURLY LEAF (CLF), a SET-domain component of Polycomb Repressive Complex 2 (PRC2), nor the resultant deposition of the histone mark H3K27me3 required for vernalization-induced FLOWERING LOCUS C (FLC) repression were affected, icu2-1 mutants exhibited unstable maintenance of the H3K27me3 level at the FLC region, which resulted in mosaic FLC de-repression after vernalization. ICU2 maintains the repressive chromatin state at additional PRC2 targets as well as at heterochromatic retroelements. In icu2-1 mutants, the subsequent binding of LIKE-HETEROCHROMATIN PROTEIN 1 (LHP1), a functional homolog of PRC1, at PRC2 targets was also reduced. We demonstrated that ICU2 facilitates histone assembly in dividing cells, suggesting a possible mechanism for ICU2-mediated epigenetic maintenance. KEY WORDS: DNA polymerase a, Epigenetic maintenance, Chromatin assemblyThe catalytic subunit of Arabidopsis DNA polymerase a ensures stable maintenance of histone modification RESEARCH ARTICLEEpigenetic maintenance by DNA pol a region in subsequent warm growing conditions by an unknown mechanism (De Lucia et al., 2008;Finnegan and Dennis, 2007). Therefore, stable inheritance of H3K27me3 and the concomitant FLC silencing are crucial for the acquisition of floral competence after vernalization.In this study, we presented new evidence that ICU2 is specifically involved in the maintenance of repressive histone marks during mitoses, but not in the mark deposition on histones, by analyzing the mitotic maintenance of vernalization memory in icu2-1 mutants. In addition, the role of ICU2 in silencing diverse chromatin loci and the functional relationship of ICU2 with PRC2 and LHP1 were also examined. Lastly, we identified a possible mechanism for ICU2-mediated epigenetic inheritance by analyzing DNA replication-dependent chromatin assembly in icu2-1 mutant plants. MATERIALS AND METHODS Plant materials, growing conditions, histochemical GUS staining and microscopyAll plants used in this study originated from the Col-0 background except for the icu2-1 (En-2), polα (C24) and clf-2 (Ler) mutants. To generate icu2-1 FRI and clf-2 FRI, each mutant allele was introduced into FRI-Col through five backcrosses. The plants were grown in either long-day (16 hour light/8 hour dark) or short-day (8 hour light/16 hour dark) ...

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Section: Roles Of Dna Replication Machinery In Epigenetic Maintenancementioning

confidence: 88%

The catalytic subunit ofArabidopsisDNA polymerase α ensures stable maintenance of histone modification

et al. 2013

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“…The MMS22L-TONSL complex is recruited to sites of RPA-coated ssDNA to promote recombination repair of damaged replication forks (31)(32)(33). The MMS22L-TONSL complex facilitates homologous recombination after DNA end resection through promoting RAD51 filament formation.…”

Section: Figure 2 Ipond-ms Identifies Proteins Enriched At Active Rementioning

confidence: 99%

Identification of Proteins at Active, Stalled, and Collapsed Replication Forks Using Isolation of Proteins on Nascent DNA (iPOND) Coupled with Mass Spectrometry

Sirbu¹,

McDonald

Dungrawala³

et al. 2013

Journal of Biological Chemistry

208

226

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Background: DNA replication and the replication stress response require the coordinated actions of many proteins. Results: iPOND coupled with mass spectrometry identified 290 proteins associated with active, stalled, or collapsed replication forks. Conclusion: iPOND-MS is a useful discovery tool. Significance: The data increase our understanding of the network of proteins involved in DNA replication and the replication stress response.

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“…These include RAD51AP1 (Wiese et al 2007) and TONSL/MMS22L (Duro et al 2010, O'Donnell et al 2010. Further analysis will shed more light on the possible interplay between these proteins and HR mechanisms underlying disorders like FA or HBOC.…”

Section: C-terminal Rad51 Binding Sitementioning

confidence: 99%

Defects in homologous recombination repair behind the human diseases: FA and HBOC

Katsuki

Takata

2016

Endocrine-Related Cancer

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Hereditary breast and ovarian cancer (HBOC) syndrome and a rare childhood disorder Fanconi anemia (FA) are caused by homologous recombination (HR) defects, and some of the causative genes overlap. Recent studies in this field have led to the exciting development of PARP inhibitors as novel cancer therapeutics and have clarified important mechanisms underlying genome instability and tumor suppression in HR-defective disorders. In this review, we provide an overview of the basic molecular mechanisms governing HR and DNA crosslink repair, highlighting BRCA2, and the intriguing relationship between HBOC and FA.

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The MMS22L-TONSL Complex Mediates Recovery from Replication Stress and Homologous Recombination

Cited by 109 publications

References 50 publications

The catalytic subunit ofArabidopsisDNA polymerase α ensures stable maintenance of histone modification

The catalytic subunit ofArabidopsisDNA polymerase α ensures stable maintenance of histone modification

Identification of Proteins at Active, Stalled, and Collapsed Replication Forks Using Isolation of Proteins on Nascent DNA (iPOND) Coupled with Mass Spectrometry

Defects in homologous recombination repair behind the human diseases: FA and HBOC

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