Histone Variants and Their Chaperones in Hematological Malignancies

Kirkiz, Ecem; Meers, Oliver; Grebien, Florian; Buschbeck, Marcus

doi:10.1097/hs9.0000000000000927

Cited by 3 publications

(2 citation statements)

References 131 publications

(280 reference statements)

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“…This study simultaneously detected DNA DSBR using neutral comet electrophoresis and immunocytochemistry. Besides its involvement in chromatin remodeling, γ-H2AX has also been associated with several cellular functions, such as DNA repair ( 12 ). In response to a DSB, γH2AX occur to initiate repair, rapidly and meticulously.…”

Section: Resultsmentioning

confidence: 99%

ARID1A is involved in DNA double-strand break repair in gastric cancer

Zhang,

Qian,

et al. 2024

J Gastrointest Oncol

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Background Defects in DNA damage repair can cause genetic mutations, which in turn can cause different types of cancers. Chromatin remodeling complexes, which help repair damaged DNA, can cause the chromatin structure to change as a result of DNA damage. ARID1A may play a role in the process of DNA damage repair, and arid1a may be related to the occurrence and development of gastric cancer (GC). This study aimed to investigate the mechanism of ARID1A regulating the DNA damage repair of gastric adenocarcinoma cell lines AGS and SGC-7901 and its effect on migration, proliferation and apoptosis. Methods The expression of ARID1A plasmid was detected by Western blot and real-time polymerase chain reaction (PCR). The effect of etoposide (ETO) on the survival rate of AGS and SGC-7901 gastric adenocarcinoma cell lines was detected by MTT assay. The DNA double-strand break model was established by ETO and then passed through the comet assay and immunofluorescence co-localization to observe DNA damage; western blot method was used to detect the effect of ARID1A on the expression of related proteins in DNA damage repair pathway in gastric adenocarcinoma cells; scratch test and colony formation experiments were used to observe ARID1A migration and proliferation of gastric adenocarcinoma cells. The flow cytometry was used to detect the effect of ARID1A on apoptosis of gastric adenocarcinoma cells. Results The expression of mRNA and protein was increased after transfection of ARID1A plasmid. ETO was confirmed by MTT assay to inhibit cell survival in a dose-dependent manner. After the DNA double-strand break model was established by ETO, the expression levels of phospho-ataxia telangiectasia mutated (p-ATM) protein increased in the overexpressed ARID1A group. Meanwhile, the overexpressed ARID1A group had a shortened tail moment, and γ-H2AX and ARID1A co-localized in the DNA damage site of the nucleus. The over-expressed ARID1A group had weaker wound healing ability, reduced number of clone formation, and increased apoptosis rate. Conclusions ARID1A may repair DNA double-strand breaks caused by ETO by p-ATM pathway; ARID1A can inhibit the migration and proliferation of gastric adenocarcinoma cells and promote apoptosis. Our findings indicate that ARID1A could serve as a therapeutic target and biomarker for GC patients.

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Section: Resultsmentioning

confidence: 99%

ARID1A is involved in DNA double-strand break repair in gastric cancer

Zhang,

Qian,

et al. 2024

J Gastrointest Oncol

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“…These variants diverge from canonical histones by single amino acid changes or inclusion/deletion of entire protein domains, thus influencing chromatin architecture and gene regulation [ 2 , 37 , 38 , 39 ]. Histone variants and their specific chaperones recruit effector proteins and chromatin remodelers that also influence gene expression [ 15 , 40 , 41 , 42 ]. For example, H3.3 is deposited by HIRA and DAXX chaperones in actively transcribed regions during normal cell growth and development [ 43 , 44 ], changing nucleosome stability [ 45 ] and altering histone PTMs [ 46 , 47 , 48 ].…”

Section: Canonical and Non-canonical Histonesmentioning

confidence: 99%

Beyond the Usual Suspects: Examining the Role of Understudied Histone Variants in Breast Cancer

Dhahri,

Saintilnord,

Chandler

et al. 2024

IJMS

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The incorporation of histone variants has structural ramifications on nucleosome dynamics and stability. Due to their unique sequences, histone variants can alter histone–histone or histone–DNA interactions, impacting the folding of DNA around the histone octamer and the overall higher-order structure of chromatin fibers. These structural modifications alter chromatin compaction and accessibility of DNA by transcription factors and other regulatory proteins to influence gene regulatory processes such as DNA damage and repair, as well as transcriptional activation or repression. Histone variants can also generate a unique interactome composed of histone chaperones and chromatin remodeling complexes. Any of these perturbations can contribute to cellular plasticity and the progression of human diseases. Here, we focus on a frequently overlooked group of histone variants lying within the four human histone gene clusters and their contribution to breast cancer.

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