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H3K9me3 DSB

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https://www.readbyqxmd.com/read/24927542/dna-double-strand-breaks-promote-methylation-of-histone-h3-on-lysine-9-and-transient-formation-of-repressive-chromatin
#1
Marina K Ayrapetov, Ozge Gursoy-Yuzugullu, Chang Xu, Ye Xu, Brendan D Price
Dynamic changes in histone modification are critical for regulating DNA double-strand break (DSB) repair. Activation of the Tip60 acetyltransferase by DSBs requires interaction of Tip60 with histone H3 methylated on lysine 9 (H3K9me3). However, how H3K9 methylation is regulated during DSB repair is not known. Here, we demonstrate that a complex containing kap-1, HP1, and the H3K9 methyltransferase suv39h1 is rapidly loaded onto the chromatin at DSBs. Suv39h1 methylates H3K9, facilitating loading of additional kap-1/HP1/suv39h1 through binding of HP1's chromodomain to the nascent H3K9me3...
June 24, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/23768498/chlamydia-infection-promotes-host-dna-damage-and-proliferation-but-impairs-the-dna-damage-response
#2
Cindrilla Chumduri, Rajendra Kumar Gurumurthy, Piotr K Zadora, Yang Mi, Thomas F Meyer
The obligate intracellular bacterial pathogen Chlamydia trachomatis (Ctr) has been associated with cervical and ovarian cancer development. However, establishment of causality and the underlying mechanisms remain outstanding. Our analysis of Ctr-induced alterations to global host histone modifications revealed distinct patterns of histone marks during acute and persistent infections. In particular, pH2AX (Ser139) and H3K9me3, hallmarks of DNA double-strand breaks (DSBs) and senescence-associated heterochromatin foci (SAHF), respectively, showed sustained upregulation during Ctr infection...
June 12, 2013: Cell Host & Microbe
https://www.readbyqxmd.com/read/23744078/kdm4b-histone-demethylase-is-a-dna-damage-response-protein-and-confers-a-survival-advantage-following-%C3%AE-irradiation
#3
Leah C Young, Darin W McDonald, Michael J Hendzel
DNA damage evokes a complex and highly coordinated DNA damage response (DDR) that is integral to the suppression of genomic instability. Double-strand breaks (DSBs) are considered the most deleterious form damage. Evidence suggests that trimethylation of histone H3 lysine 9 (H3K9me3) presents a barrier to DSB repair. Also, global levels of histone methylation are clinically predictive for several tumor types. Therefore, demethylation of H3K9 may be an important step in the repair of DSBs. The KDM4 subfamily of demethylases removes H3K9 tri- and dimethylation and contributes to the regulation of cellular differentiation and proliferation; mutation or aberrant expression of KDM4 proteins has been identified in several human tumors...
July 19, 2013: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22749149/mechanistic-links-between-atm-and-histone-methylation-codes-during-dna-repair
#4
REVIEW
Ye Xu, Chang Xu, Brendan D Price
The ataxia telangiectasia-mutated (ATM) protein kinase is the master regulator of the DNA double-strand break (DSB) repair pathway. The activation of ATM involves its recruitment to the DSB through interaction with the mre11-rad50-nbs1 complex, followed by the acetylation of ATM by the Tip60 acetyltransferase. This acetylation of ATM within its regulatory domain is essential for activating ATM's kinase activity. Further work has now revealed that Tip60 is activated through direct interaction between Tip60's chromodomain and histone H3 trimethylated on lysine 9 (H3K9me3)...
2012: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/21746811/epigenetic-tethering-of-aid-to-the-donor-switch-region-during-immunoglobulin-class-switch-recombination
#5
Beena Patricia Jeevan-Raj, Isabelle Robert, Vincent Heyer, Adeline Page, Jing H Wang, Florence Cammas, Frederick W Alt, Régine Losson, Bernardo Reina-San-Martin
Immunoglobulin class switch recombination (CSR) is initiated by double-stranded DNA breaks (DSBs) in switch regions triggered by activation-induced cytidine deaminase (AID). Although CSR correlates with epigenetic modifications at the IgH locus, the relationship between these modifications and AID remains unknown. In this study, we show that during CSR, AID forms a complex with KAP1 (KRAB domain-associated protein 1) and HP1 (heterochromatin protein 1) that is tethered to the donor switch region (Sμ) bearing H3K9me3 (trimethylated histone H3 at lysine 9) in vivo...
August 1, 2011: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/21342792/dna-repair-in-the-context-of-chromatin-new-molecular-insights-by-the-nanoscale-detection-of-dna-repair-complexes-using-transmission-electron-microscopy
#6
Claudia E Rübe, Yvonne Lorat, Nadine Schuler, Stefanie Schanz, Gunther Wennemuth, Christian Rübe
The recognition and repair of DNA double-strand breaks (DSBs) occurs in the context of highly structured chromatin. Here, we established a transmission electron microscopy (TEM) approach to localize gold-labeled DSB repair components in different chromatin environments within the intact nuclear architecture of cells in irradiated mouse tissues. The ultra-high resolution of TEM offers the intriguing possibility of detecting core components of the DNA repair machinery at the single-molecule level and visualizing their molecular interactions with specific histone modifications...
April 3, 2011: DNA Repair
https://www.readbyqxmd.com/read/20736911/evaluation-of-the-spatial-distribution-of-gammah2ax-following-ionizing-radiation
#7
Raja S Vasireddy, Michelle M Tang, Li-Jeen Mah, George T Georgiadis, Assam El-Osta, Tom C Karagiannis
An early molecular response to DNA double-strand breaks (DSBs) is phosphorylation of the Ser-139 residue within the terminal SQEY motif of the histone H2AX. This phosphorylation of H2AX is mediated by the phosphatidyl-inosito 3-kinase (PI3K) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR). The phosphorylated form of H2AX, referred to as gammaH2AX, spreads to adjacent regions of chromatin from the site of the DSB, forming discrete foci, which are easily visualized by immunofluorescence microscopy...
2010: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/19786570/loss-of-yy1-impacts-the-heterochromatic-state-and-meiotic-double-strand-breaks-during-mouse-spermatogenesis
#8
Su Wu, Yueh-Chiang Hu, Huifei Liu, Yang Shi
The progression of spermatogenesis involves global changes in chromatin structure and conformation. However, our understanding of the regulation of chromatin changes in germ cells remains limited. Here we describe both in vivo RNA interference and genetic mouse knockout studies that identify a critical role for Yin Yang 1 (YY1) in mammalian spermatogenesis. In the YY1-deficient spermatocytes, we find a significant decrease in the global level of the heterochromatin markers (H3K9me3 and HP1-gamma) and a concomitant increase in the double-strand break (DSB) signals on chromosomes (gamma-H2AX, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and Rad51) at the leptotene/zygotene stages of spermatocytes...
December 2009: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/19783983/histone-h3-methylation-links-dna-damage-detection-to-activation-of-the-tumour-suppressor-tip60
#9
Yingli Sun, Xiaofeng Jiang, Ye Xu, Marina K Ayrapetov, Lisa A Moreau, Johnathan R Whetstine, Brendan D Price
DNA double-strand break (DSB) repair involves complex interactions between chromatin and repair proteins, including Tip60, a tumour suppressor. Tip60 is an acetyltransferase that acetylates both histones and ATM (ataxia telangiectasia mutated) kinase. Inactivation of Tip60 leads to defective DNA repair and increased cancer risk. However, how DNA damage activates the acetyltransferase activity of Tip60 is not known. Here, we show that direct interaction between the chromodomain of Tip60 and histone H3 trimethylated on lysine 9 (H3K9me3) at DSBs activates the acetyltransferase activity of Tip60...
November 2009: Nature Cell Biology
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