Destabilization of linker histone H1.2 is essential for ATM activation and DNA damage repair

Li, Zhiming; Li, Yinglu; Tang, Ming; Peng, Bin; Lu, Xiaopeng; Yang, Qiong; Zhu, Qian; Hou, Tianyun; Li, Meiting; Liu, Chaohua; Wang, Lina; Xu, Xingzhi; Zhao, Ying; Wang, Haiying; Yang, Yang; Zhu, Weiguo

doi:10.1038/s41422-018-0048-0

Cited by 69 publications

(68 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanisms underlying ATM inhibition have emerged recently. It has been shown that H1.2 and Bridging Integrator 1 (BIN1) attenuate ATM activation by directly interacting with ATM [47] or by indirect mechanisms involving E2F1 [48]. Notably, HITT expression is elevated 1 h after Dox treatment, which is later than ATM activation is detected (5 min).…”

Section: Plos Biologymentioning

confidence: 99%

A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers

et al. 2020

View full text Add to dashboard Cite

Ataxia-telangiectasia mutated (ATM) is an apical kinase of the DNA damage response following DNA double-strand breaks (DSBs); however, the mechanisms of ATM activation are not completely understood. Long noncoding RNAs (lncRNAs) are a class of regulatory molecules whose significant roles in DNA damage response have started to emerge. However, how lncRNA regulates ATM activity remains unknown. Here, we identify an inhibitor of ATM activation, lncRNA HITT (HIF-1α inhibitor at translation level). Mechanistically, HITT directly interacts with ATM at the HEAT repeat domain, blocking MRE11-RAD50-NBS1 complexdependent ATM recruitment, leading to restrained homologous recombination repair and enhanced chemosensitization. Following DSBs, HITT is elevated mainly by the activation of Early Growth Response 1 (EGR1), resulting in retarded and restricted ATM activation. A reverse association between HITT and ATM activity was also detected in human colon cancer tissues. Furthermore, HITTs sensitize DNA damaging agent-induced cell death both in vitro and in vivo. These findings connect lncRNA directly to ATM activity regulation and reveal potential roles for HITT in sensitizing cancers to genotoxic treatment.

show abstract

Section: Plos Biologymentioning

confidence: 99%

A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In fact, H. pylori infection causes H3 Ser10 dephosphorylation and other histone modification changes that consequently affect the gastric epithelium and ultimately affect the pathogenicity of the bacterium (Ding et al 2010;Fehri et al 2009). Because several studies have shown that chromatin modifications, including certain types of histone modifications, are mechanistically and functionally relevant to ATM activation (Li et al 2018), it is tempting to speculate that H. pylori can also activate ATM through sophisticated histone modifications. These findings demonstrate that H. pylori infection triggers ATM activation through both activating ATM activity and increasing ATM protein levels.…”

Section: Helicobacter Pylori Triggers Atm Activationmentioning

confidence: 99%

Helicobacter pylori infection induced genome instability and gastric cancer

Liu

Irfan

et al. 2020

GENOME INSTAB. DIS.

Self Cite

View full text Add to dashboard Cite

Genome stability and integrity are constantly challenged by exogenous insults such as bacterial infections. When genome stability is perturbed, oncogenic transformation can ensue. Helicobacter pylori (H. pylori) infection is a driving factor of gastric cancer, which is the third leading cause of cancer-related mortality worldwide. Mechanistically, H. pylori infection drives inflammation and directly or indirectly induces DNA damage such as oxidative damage and double-strand breaks (DSBs) in host cells. In addition, the resulting genetic and/or epigenetic perturbations alter the choice of DNA repair pathways. These changes result in imprecise DNA repair, genomic instability as well as chromosomal aberrations that eventually lead to gastric carcinogenesis. In this review, we summarize the mechanisms how H. pylori infection cause DNA damage and alter the DNA damage response pathways in host cells. We highlight the relationship between H. pylori infection and genomic instability that can lead to gastric cancer and propose a potential strategy to interrupt gastric carcinogenesis.

show abstract

“…Maintaining the integrity of the genome of mammalian preimplantation embryos, which can be damaged by both internal and external factors, is critical for normal preimplantation and subsequent development. Epigenetic factors contribute to the maintenance of genome stability, e.g., by preventing excessive activation of ATM by linker histone H1.2 and promoting DNA damage repair by histone-modifying enzymes G9a or SETD8 [ 5 , 7 , 14 ]. However, few studies have examined the relationship between epigenetics and genomic integrity during mouse preimplantation development.…”

Section: Discussionmentioning

confidence: 99%

“…Epigenetic alterations such as histone modifications and localization of linker histones contribute to DNA damage repair [ 5 , 6 , 7 ]. Histone H4K20 methylation is conserved from yeast to human; H4K20 can be monomethylated by SETD8/PR-SET7 and di- and trimethylated by SUV4-20H1 and SUV4-20H2 [ 8 , 9 , 10 , 11 ].…”

mentioning

confidence: 99%

H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos

Shikata

Yamamoto

Honda

et al. 2020

Journal of Reproduction and Development

View full text Add to dashboard Cite

Maintaining genomic integrity in mammalian early embryos, which are deficient in DNA damage repair, is critical for normal preimplantation and subsequent development. Abnormalities in DNA damage repair in preimplantation embryos can cause not only developmental arrest, but also diseases such as congenital disorders and cancers. Histone H4 lysine 20 monomethylation (H4K20me1) is involved in DNA damage repair and regulation of gene expression. However, little is known about the role of H4K20me1 during mouse preimplantation development. In this study, we revealed that H4K20me1 mediated by SETD8 is involved in maintaining genomic integrity. H4K20me1 was present throughout preimplantation development. In addition, reduction in the level of H4K20me1 by inhibition of SETD8 activity or a dominant-negative mutant of histone H4 resulted in developmental arrest at the S/G2 phase and excessive accumulation of DNA double-strand breaks. Together, our results suggest that H4K20me1, a type of epigenetic modification, is associated with the maintenance of genomic integrity and is essential for preimplantation development. A better understanding of the mechanisms involved in maintaining genome integrity during preimplantation development could contribute to advances in reproductive medicine and technology.

show abstract

Destabilization of linker histone H1.2 is essential for ATM activation and DNA damage repair

Cited by 69 publications

References 64 publications

A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers

A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers

Helicobacter pylori infection induced genome instability and gastric cancer

H4K20 monomethylation inhibition causes loss of genomic integrity in mouse preimplantation embryos

Contact Info

Product

Resources

About