Human CHD1 is required for early DNA-damage signaling and is uniquely regulated by its N terminus

Zhou, Jia; Li, Jiaqi; Serafim, Rodolfo Bortolozo; Ketchum, Steven; Ferreira, Catarina G.; Liu, Jia; Coe, Kathryn A.; Price, Brendan D.; Yusufzai, Timur

doi:10.1093/nar/gky128

Cited by 35 publications

(43 citation statements)

References 37 publications

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“…As a result it is somewhat surprising that the area of contact between the chromodomains and DNABD is so small. It is possible that additional regions of Chd1 including the Nterminus that is not resolved in the density map also contribute to this interaction as suggested by previous studies of Chd1 proteins (Liu et al, 2015;Zhou et al, 2018) (Sundaramoorthy et al, 2017).…”

Section: Resultsmentioning

confidence: 90%

Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

Sundaramoorthy

Hughes

Mkami

et al. 2018

Preprint

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ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the yeast Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

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Section: Resultsmentioning

confidence: 90%

Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

Sundaramoorthy

Hughes

Mkami

et al. 2018

Preprint

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“…PARP1, CHD2, and H3.3 regulate the assembly of NHEJ complexes at broken chromosomes to promote efficient DNA repair (Luijsterburg et al, 2016). Targeted disruption of the CHD1 gene in human cells leads to a defect in DSB repair via homologous recombination, resulting in hypersensitivity to ionizing radiation and in increased error-prone NHEJ repair for DSB repair (Kari et al, 2016;Shenoy et al, 2017;Zhou et al, 2018). We have shown that null mutations of Drosophila Chd1 cause hypersensitivity to ionizing radiation at the third instar larval stage, suggesting that Drosophila CHD1 is also involved in DSB repair.…”

Section: Itroductionmentioning

confidence: 90%

The role of aTp-dependent chromatin remodeling factors in chromatin assembly in vivo

Ильина¹,

Konev²

2019

Vestn. VOGiS

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Chromatin assembly is a fundamental process essential for chromosome duplication subsequent to DNA replication. In addition, histone removal and incorporation take place constantly throughout the cell cycle in the course of DNA-utilizing processes, such as transcription, damage repair or recombination. In vitro studies have revealed that nucleosome assembly relies on the combined action of core histone chaperones and ATP-utilizing molecular motor proteins such as ACF or CHD1. Despite extensive biochemical characterization of ATP-dependent chromatin assembly and remodeling factors, it has remained unclear to what extent nucleosome assembly is an ATP-dependent process in vivo. Our original and published data about the functions of ATP-dependent chromatin assembly and remodeling factors clearly demonstrated that these proteins are important for nucleosome assembly and histone exchange in vivo. During male pronucleus reorganization after fertilization CHD1 has a critical role in the genomescale, replication-independent nucleosome assembly involving the histone variant H3.3. Thus, the molecular motor proteins, such as CHD1, function not only in the remodeling of existing nucleosomes but also in de novo nucleosome assembly from DNA and histones in vivo. ATP-dependent chromatin assembly and remodeling factors have been implicated in the process of histone exchange during transcription and DNA repair, in the maintenance of centromeric chromatin and in the loading and remodeling of nucleosomes behind a replication fork. Thus, chromatin remodeling factors are involved in the processes of both replication-dependent and replication-independent chromatin assembly. The role of these proteins is especially prominent in the processes of large-scale chromatin reorganization; for example, during male pronucleus formation or in DNA repair. Together, ATP-dependent chromatin assembly factors, histone chaperones and chromatin modifying enzymes form a “chromatin integrity network” to ensure proper maintenance and propagation of chromatin landscape.

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“… 2018 ; Zhou et al. 2018 ). In the present study, we observed histone H2A release from chromatin after empty vector-transfected and mutant BRG1-transfected cells were treated with ETO ( Figure 3 (B)).…”

Section: Discussionmentioning

confidence: 99%

BRG1 Promotes chromatin remodeling around DNA damage sites

Chen

Lü

et al. 2018

Animal Cells and Systems

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Chromatin remodeling complexes play important roles in various DNA metabolism processes, including DNA damage repair. BRG1 is the core subunit of the SWI/SNF complex, which plays critical roles in cell cycle regulation, cell development, cell differentiation, and tumorigenesis. In the present study, we report that BRG1 depletion increased the percentage of apoptotic cells in etoposide-treated cells. Moreover, western blotting and immunofluorescence data showed that BRG1 depletion decreased H2AX phosphorylation and caused defective phosphorylated histone H2AX (γH2AX) clearance. Furthermore, we found that in both SW13 and U2OS cells, BRG1 expression could increase the sensitivity of genomic DNA to micrococcal nuclease (MNase) and facilitate chromatin relaxation around DNA damage sites. Thus, the results provide evidence that BRG1 plays an important role in early DNA damage repair by remodeling the chromatin structure near DNA damage sites.

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Human CHD1 is required for early DNA-damage signaling and is uniquely regulated by its N terminus

Cited by 35 publications

References 37 publications

Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

The role of aTp-dependent chromatin remodeling factors in chromatin assembly in vivo

BRG1 Promotes chromatin remodeling around DNA damage sites

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