scholarly journals Structure Change from β -Strand and Turn to α -Helix in Histone H2A-H2B Induced by DNA Damage Response

2016 ◽  
Vol 111 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Yudai Izumi ◽  
Kentaro Fujii ◽  
Frank Wien ◽  
Chantal Houée-Lévin ◽  
Sandrine Lacombe ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Structure Change ◽  
Histone H2a ◽  
Damage Response ◽  
Α Helix

scholarly journals DNA damage response induces structural alterations in histone H3–H4

2017 ◽  
Vol 58 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Yudai Izumi ◽  
Kentaro Fujii ◽  
Satoshi Yamamoto ◽  
Koichi Matsuo ◽  
Hirofumi Namatame ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Histone H3 ◽  
Structural Alteration ◽  
Histone H2a ◽  
Structural Alterations ◽  
X Ray ◽  
Damage Response ◽  
Α Helix

Abstract Synchrotron-radiation circular-dichroism spectroscopy was used to reveal that the DNA damage response induces a decrement of α-helix and an increment of β-strand contents of histone H3–H4 extracted from X-ray–irradiated human HeLa cells. The trend of the structural alteration was qualitatively opposite to that of our previously reported results for histone H2A–H2B. These results strongly suggest that histones share roles in DNA damage responses, particularly in DNA repair processes and chromatin remodeling, via a specific structural alteration of each histone.

scholarly journals Dephosphorylation of the C-terminal Tyrosyl Residue of the DNA Damage-related Histone H2A.X Is Mediated by the Protein Phosphatase Eyes Absent

2009 ◽  
Vol 284 (24) ◽  
pp. 16066-16070 ◽  
Author(s):  
Navasona Krishnan ◽  
Dae Gwin Jeong ◽  
Suk-Kyeong Jung ◽  
Seong Eon Ryu ◽  
Andrew Xiao ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Mammalian Cells ◽  
Protein Tyrosine Phosphatases ◽  
Histone H2a ◽  
Eyes Absent ◽  
Damage Repair ◽  
Damage Response

In mammalian cells, the DNA damage-related histone H2A variant H2A.X is characterized by a C-terminal tyrosyl residue, Tyr-142, which is phosphorylated by an atypical kinase, WSTF. The phosphorylation status of Tyr-142 in H2A.X has been shown to be an important regulator of the DNA damage response by controlling the formation of γH2A.X foci, which are platforms for recruiting molecules involved in DNA damage repair and signaling. In this work, we present evidence to support the identification of the Eyes Absent (EYA) phosphatases, protein-tyrosine phosphatases of the haloacid dehalogenase superfamily, as being responsible for dephosphorylating the C-terminal tyrosyl residue of histone H2A.X. We demonstrate that EYA2 and EYA3 displayed specificity for Tyr-142 of H2A.X in assays in vitro. Suppression of eya3 by RNA interference resulted in elevated basal phosphorylation and inhibited DNA damage-induced dephosphorylation of Tyr-142 of H2A.X in vivo. This study provides the first indication of a physiological substrate for the EYA phosphatases and suggests a novel role for these enzymes in regulation of the DNA damage response.

scholarly journals Nucleotide excision repair–induced H2A ubiquitination is dependent on MDC1 and RNF8 and reveals a universal DNA damage response

2009 ◽  
Vol 186 (6) ◽  
pp. 835-847 ◽  
Author(s):  
Jurgen A. Marteijn ◽  
Simon Bekker-Jensen ◽  
Niels Mailand ◽  
Hannes Lans ◽  
Petra Schwertman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Nucleotide Excision Repair ◽  
Dna Damage Response ◽  
Excision Repair ◽  
Strand Break ◽  
Epigenetic Mark ◽  
Histone H2a ◽  
Nucleotide Excision ◽  
Damage Response ◽  
Damaged Dna

Chromatin modifications are an important component of the of DNA damage response (DDR) network that safeguard genomic integrity. Recently, we demonstrated nucleotide excision repair (NER)–dependent histone H2A ubiquitination at sites of ultraviolet (UV)-induced DNA damage. In this study, we show a sustained H2A ubiquitination at damaged DNA, which requires dynamic ubiquitination by Ubc13 and RNF8. Depletion of these enzymes causes UV hypersensitivity without affecting NER, which is indicative of a function for Ubc13 and RNF8 in the downstream UV–DDR. RNF8 is targeted to damaged DNA through an interaction with the double-strand break (DSB)–DDR scaffold protein MDC1, establishing a novel function for MDC1. RNF8 is recruited to sites of UV damage in a cell cycle–independent fashion that requires NER-generated, single-stranded repair intermediates and ataxia telangiectasia–mutated and Rad3-related protein. Our results reveal a conserved pathway of DNA damage–induced H2A ubiquitination for both DSBs and UV lesions, including the recruitment of 53BP1 and Brca1. Although both lesions are processed by independent repair pathways and trigger signaling responses by distinct kinases, they eventually generate the same epigenetic mark, possibly functioning in DNA damage signal amplification.

scholarly journals Structure and DNA damage-dependent derepression mechanism for the XRE family member DG-DdrO

2019 ◽  
Vol 47 (18) ◽  
pp. 9925-9933 ◽  
Author(s):  
Huizhi Lu ◽  
Liangyan Wang ◽  
Shengjie Li ◽  
Chaoming Pan ◽  
Kaiying Cheng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Dna Damage Response ◽  
Hydrophobic Interactions ◽  
Salt Bridge ◽  
Damage Response ◽  
Promoter Dna ◽  
Α Helix ◽  
Oppositely Charged ◽  
Insight Into

Abstract DdrO is an XRE family transcription repressor that, in coordination with the metalloprotease PprI, is critical in the DNA damage response of Deinococcus species. Here, we report the crystal structure of Deinococcus geothermalis DdrO. Biochemical and structural studies revealed the conserved recognizing α-helix and extended dimeric interaction of the DdrO protein, which are essential for promoter DNA binding. Two conserved oppositely charged residues in the HTH motif of XRE family proteins form salt bridge interactions that are essential for promoter DNA binding. Notably, the C-terminal domain is stabilized by hydrophobic interactions of leucine/isoleucine-rich helices, which is critical for DdrO dimerization. Our findings suggest that DdrO is a novel XRE family transcriptional regulator that forms a distinctive dimer. The structure also provides insight into the mechanism of DdrO-PprI-mediated DNA damage response in Deinococcus.

Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response

2016 ◽  
Vol 16 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Takayo Fukuda ◽  
Tomoko Tsuruga ◽  
Takako Kuroda ◽  
Hiroyuki Nishikawa ◽  
Tomohiko Ohta
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Histone H2a ◽  
Functional Link ◽  
Damage Response

scholarly journals Modified chromosome structure caused by phosphomimetic H2A modulates the DNA damage response by increasing chromatin mobility in yeast

2021 ◽  
Vol 134 (6) ◽  
Author(s):  
Fabiola García Fernández ◽  
Brenda Lemos ◽  
Yasmine Khalil ◽  
Renaud Batrin ◽  
James E. Haber ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Structural Changes ◽  
Sharp Decrease ◽  
Histone H2a ◽  
End Joining ◽  
Chromatin Dynamics ◽  
Damage Response ◽  
Chromatin Structural ◽  
Non Homologous End Joining

ABSTRACT In budding yeast and mammals, double-strand breaks (DSBs) trigger global chromatin mobility together with rapid phosphorylation of histone H2A over an extensive region of the chromatin. To assess the role of H2A phosphorylation in this response to DNA damage, we have constructed strains where H2A has been mutated to the phosphomimetic H2A-S129E. We show that mimicking H2A phosphorylation leads to an increase in global chromatin mobility in the absence of DNA damage. The intrinsic chromatin mobility of H2A-S129E is not due to downstream checkpoint activation, histone degradation or kinetochore anchoring. Rather, the increased intrachromosomal distances observed in the H2A-S129E mutant are consistent with chromatin structural changes. Strikingly, in this context the Rad9-dependent checkpoint becomes dispensable. Moreover, increased chromatin dynamics in the H2A-S129E mutant correlates with improved DSB repair by non-homologous end joining and a sharp decrease in interchromosomal translocation rate. We propose that changes in chromosomal conformation due to H2A phosphorylation are sufficient to modulate the DNA damage response and maintain genome integrity. This article has an associated First Person interview with the first author of the paper.

scholarly journals Diverse Roles for Histone H2A Modifications in DNA Damage Response Pathways in Yeast

Genetics ◽  
2006 ◽  
Vol 176 (1) ◽  
pp. 15-25 ◽  
Author(s):  
John D. Moore ◽  
Oya Yazgan ◽  
Yeganeh Ataian ◽  
Jocelyn E. Krebs
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Histone H2a ◽  
Damage Response

scholarly journals Crosstalk between H2A variant-specific modifications impacts vital cell functions

PLoS Genetics ◽  
2021 ◽  
Vol 17 (6) ◽  
pp. e1009601
Author(s):  
Anna Schmücker ◽  
Bingkun Lei ◽  
Zdravko J. Lorković ◽  
Matías Capella ◽  
Sigurd Braun ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Mutual Exclusion ◽  
Histone H2a ◽  
Cell Functions ◽  
Vital Cell ◽  
Damage Response ◽  
Cycle Dependent ◽  
Selection Of

Selection of C-terminal motifs participated in evolution of distinct histone H2A variants. Hybrid types of variants combining motifs from distinct H2A classes are extremely rare. This suggests that the proximity between the motif cases interferes with their function. We studied this question in flowering plants that evolved sporadically a hybrid H2A variant combining the SQ motif of H2A.X that participates in the DNA damage response with the KSPK motif of H2A.W that stabilizes heterochromatin. Our inventory of PTMs of H2A.W variants showed that in vivo the cell cycle-dependent kinase CDKA phosphorylates the KSPK motif of H2A.W but only in absence of an SQ motif. Phosphomimicry of KSPK prevented DNA damage response by the SQ motif of the hybrid H2A.W/X variant. In a synthetic yeast expressing the hybrid H2A.W/X variant, phosphorylation of KSPK prevented binding of the BRCT-domain protein Mdb1 to phosphorylated SQ and impaired response to DNA damage. Our findings illustrate that PTMs mediate interference between the function of H2A variant specific C-terminal motifs. Such interference could explain the mutual exclusion of motifs that led to evolution of H2A variants.

scholarly journals Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation

2010 ◽  
Vol 9 (1) ◽  
pp. 34 ◽  
Author(s):  
Junya Kobayashi ◽  
Akihiro Kato ◽  
Yosuke Ota ◽  
Reiko Ohba ◽  
Kenshi Komatsu
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Histone H2a ◽  
Damage Response

scholarly journals Writing Histone Monoubiquitination in Human Malignancy—The Role of RING Finger E3 Ubiquitin Ligases

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 67 ◽  
Author(s):  
Deborah J. Marsh ◽  
Kristie-Ann Dickson
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Ring Finger ◽  
Ubiquitin Ligases ◽  
Covalent Attachment ◽  
Transcriptional Elongation ◽  
E3 Ubiquitin Ligases ◽  
Histone H2a ◽  
Damage Response ◽  
Active Transcription

There is growing evidence highlighting the importance of monoubiquitination as part of the histone code. Monoubiquitination, the covalent attachment of a single ubiquitin molecule at specific lysines of histone tails, has been associated with transcriptional elongation and the DNA damage response. Sites function as scaffolds or docking platforms for proteins involved in transcription or DNA repair; however, not all sites are equal, with some sites resulting in actively transcribed chromatin and others associated with gene silencing. All events are written by E3 ubiquitin ligases, predominantly of the RING (really interesting new gene) finger type. One of the most well-studied events is monoubiquitination of histone H2B at lysine 120 (H2Bub1), written predominantly by the RING finger complex RNF20-RNF40 and generally associated with active transcription. Monoubiquitination of histone H2A at lysine 119 (H2AK119ub1) is also well-studied, its E3 ubiquitin ligase constituting part of thePolycomb Repressor Complex 1 (PRC1), RING1B-BMI1, associated with transcriptional silencing. Both modifications are activated as part of the DNA damage response. Histone monoubiquitination is a key epigenomic event shaping the chromatin landscape of malignancy and influencing how cells respond to DNA damage. This review discusses a number of these sites and the E3 RING finger ubiquitin ligases that write them.

Sign in / Sign up

Export Citation Format

Share Document