Opposing ISWI- and CHD-class chromatin remodeling activities orchestrate heterochromatic DNA repair

Klement, Karolin; Luijsterburg, Martijn S.; Pinder, Jordan; Cena, Chad S.; Nero, Victor Del; Wintersinger, Christopher M.; Dellaire, Graham; Attikum, Haico van; Goodarzi, Aaron A.

doi:10.1083/jcb.201405077

Cited by 66 publications

(82 citation statements)

References 48 publications

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“…Heterochromatin may therefore present a barrier to efficient DSB repair by the cell. Consequently, DSB repair in heterochromatin involves a unique mechanism in which phosphorylation of the KAP-1 repressor by the ATM kinase 19; 20 releases the CHD3 remodeling ATPase from the damaged chromatin 48; 54; 55 . CHD3 may oppose the activity of an ISWI complex, comprised of the SNF2H catalytic sub-unit and the ACF1 protein 54 .…”

Section: Nucleosome Dynamics and Dsb Repairmentioning

confidence: 99%

“…Consequently, DSB repair in heterochromatin involves a unique mechanism in which phosphorylation of the KAP-1 repressor by the ATM kinase 19; 20 releases the CHD3 remodeling ATPase from the damaged chromatin 48; 54; 55 . CHD3 may oppose the activity of an ISWI complex, comprised of the SNF2H catalytic sub-unit and the ACF1 protein 54 . Phosphorylation of KAP-1 and release of CHD3 at DSBs leads to significant relaxation of the chromatin 19; 48; 54 and is required for efficient DSB repair in heterochromatin.…”

Section: Nucleosome Dynamics and Dsb Repairmentioning

confidence: 99%

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Patching Broken DNA: Nucleosome Dynamics and the Repair of DNA Breaks

Gürsoy-Yüzügüllü

House

Price

2016

Journal of Molecular Biology

116

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The ability of cells to detect and repair DNA double-strand breaks (DSBs) is dependent on reorganization of the surrounding chromatin structure by chromatin remodeling complexes. These complexes promote access to the site of DNA damage, facilitate processing of the damaged DNA and, importantly, are essential to repackage the repaired DNA. Here, we will review the chromatin remodeling steps which occur immediately after DSB production and which prepare the damaged chromatin template for processing by the DSB repair machinery. DSBs promote rapid accumulation of repressive complexes, including HP1, the NuRD complex, H2A.Z and histone methyltransferases at the DSB. This shift to a repressive chromatin organization may be important to inhibit local transcription and limit mobility of the break, and to maintain the DNA ends in close contact. Subsequently, the repressive chromatin is rapidly dismantled through a mechanism involving dynamic exchange of the histone variant H2A.Z. H2A.Z removal at DSBs alters the acidic patch on the nucleosome surface, promoting acetylation of the H4 tail (by the NuA4-Tip60 complex) and shifting the chromatin to a more open structure. Further, H2A.Z removal promotes chromatin ubiquitination and recruitment of additional DSB repair proteins to the break. Modulation of the nucleosome surface and nucleosome function during DSB repair therefore plays a vital role in processing of DNA breaks. Further, the nucleosome surface may function as a central hub during DSB repair, directing specific patterns of histone modification, recruiting DNA repair proteins and modulating chromatin packing during processing of the damaged DNA template.

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Section: Nucleosome Dynamics and Dsb Repairmentioning

confidence: 99%

Section: Nucleosome Dynamics and Dsb Repairmentioning

confidence: 99%

Patching Broken DNA: Nucleosome Dynamics and the Repair of DNA Breaks

Gürsoy-Yüzügüllü

House

Price

2016

Journal of Molecular Biology

116

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“…The phosphorylation of the chromatin-associated KAP-1 can disrupt the interaction of SUMOylated KAP-1 with CHD3 on chromatin [94,95]. CHD3, a catalytic subunit of the NuRD chromatin-remodeling complex, inhibits heterochromatin decondensation possibly by opposing the chromatin-remodeling activities of an imitation switch (ISWI) complex [95]. The disassociation of CHD3 from SUMOylated KAP-1 releases this inhibitory effect, thus promoting the relaxation of heterochromatin [74,94,95].…”

Section: Heterochromatic Response To Dsbsmentioning

confidence: 99%

“…By concentrating MRN and ATM at the sites of irradiationinduced DSBs, 53BP1 may enhance ATM-mediated phosphorylation of KAP-1 [74]. The phosphorylation of the chromatin-associated KAP-1 can disrupt the interaction of SUMOylated KAP-1 with CHD3 on chromatin [94,95]. CHD3, a catalytic subunit of the NuRD chromatin-remodeling complex, inhibits heterochromatin decondensation possibly by opposing the chromatin-remodeling activities of an imitation switch (ISWI) complex [95].…”

Section: Heterochromatic Response To Dsbsmentioning

confidence: 99%

“…CHD3, a catalytic subunit of the NuRD chromatin-remodeling complex, inhibits heterochromatin decondensation possibly by opposing the chromatin-remodeling activities of an imitation switch (ISWI) complex [95]. The disassociation of CHD3 from SUMOylated KAP-1 releases this inhibitory effect, thus promoting the relaxation of heterochromatin [74,94,95]. As the DNA ends in heterochromatin can also be bound by Ku70/ Ku80 and RPA, their respective PIKK partner DNA-PKcs and ATR could be recruited and activated to phosphorylate KAP-1.…”

Section: Heterochromatic Response To Dsbsmentioning

confidence: 99%

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Buried territories: heterochromatic response to DNA double-strand breaks

Feng¹,

Xiang²,

Kong³

et al. 2016

ABBS

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Cellular response to DNA double-strand breaks (DSBs), the most deleterious type of DNA damage, is highly influenced by higher-order chromatin structure in eukaryotic cells. Compared with euchromatin, the compacted structure of heterochromatin not only protects heterochromatic DNA from damage, but also adds an extra layer of control over the response to DSBs occurring in heterochromatin. One key step in this response is the decondensation of heterochromatin structure. This decondensation process facilitates the DNA damage signaling and promotes proper heterochromatic DSB repair, thus helping to prevent instability of heterochromatic regions of genomes. This review will focus on the functions of the ataxia telangiectasia mutated (ATM) signaling cascade involving ATM, heterochromatin protein 1 (HP1), Krüppel-associated box (KRAB)-associated protein-1 (KAP-1), tat-interacting protein 60 (Tip60), and many other protein factors in DSB-induced decondensation of heterochromatin and subsequent repair of heterochromatic DSBs. As some subsets of DSBs may be repaired in heterochromatin independently of the ATM signaling, a possible repair model is also proposed for ATM-independent repair of these heterochromatic DSBs.

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Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

Alendar

2023

Encyclopedia of Life Sciences

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Vital processes such as transcription, repair, replication and recombination continuously shape cellular chromatin landscape. The chromodomain helicase DNA‐binding (CHD) family of enzymes regulate chromatin dynamics by utilising energy from ATP hydrolysis to alter nucleosomal position, structure and composition, thereby modulating accessibility of the underlying DNA sequence. The CHD enzymes are highly conserved in evolution, and genetic studies in fungi, plants and animals demonstrate their critical roles in regulation of cellular identity and fate and organismal development. Advances in genomic studies over the past two decades led to the identification of frequent DNA copy‐number alterations, mutations and aberrant expression of CHDs in human malignancies and various disorders, highlighting their importance as relevant biomarkers or targets for therapeutic intervention. Key Concepts CHD family of enzymes (CHD1‐9) are evolutionary conserved ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes, such as transcription, replication and repair. They are critical for normal organismal development and are frequently mutated in human disorders and cancers. Chromodomain helicase DNA‐binding proteins (CHD1‐9) are evolutionary conserved family of ATP‐dependent chromatin remodelers that mobilise nucleosomes to regulate DNA‐templated processes such as transcription, replication and DNA repair. CHD enzymes share a common domain structure: two N‐terminal chromodomains, a central ATPase/helicase domain, and a C‐terminal DNA‐binding domain. CHD proteins play crucial roles in diverse cellular processes, including embryonic development, stem cell maintenance and differentiation, and tissue‐specific gene expression. Dysregulation of CHD proteins has been associated with various human diseases, including cancer and neurodevelopmental disorders. CHD proteins are attractive targets for the development of new therapies for diseases associated with chromatin dysfunction. Understanding the molecular mechanisms underlying the function of CHD proteins may pave the way for the development of new drugs that target these proteins and improve the treatment of a variety of human diseases.

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Opposing ISWI- and CHD-class chromatin remodeling activities orchestrate heterochromatic DNA repair

Abstract: Chromatin compaction mediated by CHD3.1 must be counteracted by ACF1–SNF2H and RNF20 in order to allow DNA double-strand break repair in heterochromatin of postreplicative cells.

Cited by 66 publications

References 48 publications

Patching Broken DNA: Nucleosome Dynamics and the Repair of DNA Breaks

Patching Broken DNA: Nucleosome Dynamics and the Repair of DNA Breaks

Buried territories: heterochromatic response to DNA double-strand breaks

Rise of the Chromodomain Helicase DNA‐Binding (CHD) Chromatin Remodelling Machines

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