Chromatin modification and NBS1: their relationship in DNA double-strand break repair

Saito, Yuichiro; Zhou, Hui; Kobayashi, Junya

doi:10.1266/ggs.15-00010

Cited by 14 publications

(25 citation statements)

References 110 publications

(146 reference statements)

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“…Hence NHEJ is known to be an error-prone DSB repair mechanism, leading to nucleotide loss. In contrast, during HR repair, the non-damaged homologous DNA region is used as a template for the repair of DSB regions, which is why HR is an error-free DSB repair mechanism [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Their cellular phenotypes are similar as well, showing radiation hypersensitivity, chromosome instability, and radiation-resistant DNA synthesis, and it was suggested that the genes responsible for these diseases ( ATM in A-T and NBS1 in NBS) play physical or functional roles during the DSB-induced response. The product of ATM is a protein kinase, while the product of NBS1 is an adaptor protein that regulates DDRs through the formation of a protein complex [ 1 , 2 ]. ATM kinase is activated in response to DSBs and has a fundamental role in the regulation of cell cycle checkpoints through the phosphorylation of DDR proteins, including p53, Chk2 and NBS1 [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…The product of human NBS1 is a 754-amino acid (a.a.) protein that contains several functional domains, mainly located in the N- and C-termini. The N-terminus includes a forkhead-associated (FHA) domain and two BRCA1 C-terminus (BRCT) domains, which contribute to the binding of several phosphorylated proteins [ 1 ]. The C-terminus of NBS1 protein interacts with several functional proteins as well, including ATM and MRE11, and these interactions are vital for various DNA damage responses [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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NBS1 is regulated by two kind of mechanisms: ATM-dependent complex formation with MRE11 and RAD50, and cell cycle–dependent degradation of protein

Zhou

Kawamura

Yanagihara

et al. 2017

Journal of Radiation Research

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Nijmegen breakage syndrome (NBS), a condition similar to Ataxia-Telangiectasia (A-T), is a radiation-hypersensitive genetic disorder showing chromosomal instability, radio-resistant DNA synthesis, immunodeficiency, and predisposition to malignances. The product of the responsible gene, NBS1, forms a complex with MRE11 and RAD50 (MRN complex). The MRN complex is necessary for the DNA damage–induced activation of ATM. However, the regulation of MRN complex formation is still unclear. Here, we investigated the regulatory mechanisms of MRN complex formation. We used an immunoprecipitation assay to determine whether levels of the MRN complex were increased by radiation-induced DNA damage and found that the levels of these proteins and their mRNAs did not increase. ATM-dependent phosphorylation of NBS1 contributed to the DNA damage–induced MRN complex formation. However, pre-treatment of cells with an ATM-specific inhibitor did not affect homologous recombination (HR) and non-homologous end-joining (NHEJ) repair. G0 phase cells, decreasing NBS1 and HR activity but not NHEJ, gained HR-related chromatin association of RAD51 by overexpression of NBS1, suggesting that the amount of NBS1 may be important for repressing accidental activation of HR. These evidences suggest that NBS1 is regulated by two kind of mechanisms: complex formation dependent on ATM, and protein degradation mediated by an unknown MG132-resistant pathway. Such regulation of NBS1 may contribute to cellular responses to double-strand breaks.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NBS1 is regulated by two kind of mechanisms: ATM-dependent complex formation with MRE11 and RAD50, and cell cycle–dependent degradation of protein

Zhou

Kawamura

Yanagihara

et al. 2017

Journal of Radiation Research

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“…Polη can replicate 8-oxoguanine lesions efficiently and accurately by inserting a C opposite to the damage site (22). Polη can also bypass other lesions such as (6–4) TT photoproducts (23), O-6-methylguanine (24), abasic sites (25), and DNA double-strand breaks (26). In S. cerevisiae , Polη is recruited to stalled replication forks by its physical interaction with monoubiquitinated PCNA (27).…”

Section: Introductionmentioning

confidence: 99%

Lsm12 mediates Pol·q deubiquitination to help Saccharomyces cerevisiae resist oxidative stress

Yao

Shi²,

Chen

et al. 2018

Preprint

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15In Saccharomyces cerevisiae, the Y-family DNA polymerase η (Polη) regulates genome stability 16 in response to different forms of environmental stress by translesion DNA synthesis. To elucidate 17 the role of Polη in oxidative stress-induced DNA damage, we deleted or overexpressed the 18 corresponding gene RAD30, and used transcriptome analysis to screen the potential genes 19 associated with RAD30 to respond to DNA damage. Under 2 mM H 2 O 2 , deletion of RAD30 20 resulted in a 2.2-fold decrease in survival and a 2.8-fold increase in DNA damage, whereas 21 overexpression of RAD30 increased survival and decreased DNA damage by 1.2-and 1.4-fold, 22 IMPORTANCE 34Polη was shown to be critical for cell growth in the yeast Saccharomyces cerevisiae, and deletion 35 of its corresponding gene RAD30 caused a severe growth defect under exposure to oxidative 36 stress with 2 mM H 2 O 2 . Furthermore, we found that Lsm12 physically interacts with Polη and 37 promotes Polη deubiquitination and recruitment. Overall, these findings indicate Lsm12 as a 38 novel regulator mediating Polη deubiquitination that regulates its recruitment in response to 39 DNA damage induced by oxidative stress. 40

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“…Pol can replicate 8-oxoguanine lesions efficiently and accurately by inserting a C opposite of the damage site (22). Pol can also bypass other lesions, such as TT photoproducts (23), O-6-methylguanine (24), abasic sites (25), and DNA doublestrand breaks (26). In S. cerevisiae, Pol is recruited to stalled replication forks by its physical interaction with monoubiquitinated PCNA (27).…”

mentioning

confidence: 99%

Lsm12 Mediates Deubiquitination of DNA Polymerase η To Help Saccharomyces cerevisiae Resist Oxidative Stress

Yao

Shi

et al. 2019

Appl Environ Microbiol

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In Saccharomyces cerevisiae, the Y family DNA polymerase (Pol) regulates genome stability in response to different forms of environmental stress by translesion DNA synthesis. To elucidate the role of Pol in oxidative stress-induced DNA damage, we deleted or overexpressed the corresponding gene RAD30 and used transcriptome analysis to screen the potential genes associated with RAD30 to respond to DNA damage. Under 2 mM H 2 O 2 treatment, the deletion of RAD30 resulted in a 2.2-fold decrease in survival and a 2.8-fold increase in DNA damage, whereas overexpression of RAD30 increased survival and decreased DNA damage by 1.2-and 1.4-fold, respectively, compared with the wild-type strain. Transcriptome and phenotypic analyses identified Lsm12 as a main factor involved in oxidative stress-induced DNA damage. Deleting LSM12 caused growth defects, while its overexpression enhanced cell growth under 2 mM H 2 O 2 treatment. This effect was due to the physical interaction of Lsm12 with the UBZ domain of Pol to enhance Pol deubiquitination through Ubp3 and consequently promote Pol recruitment. Overall, these findings demonstrate that Lsm12 is a novel regulator mediating Pol deubiquitination to promote its recruitment under oxidative stress. Furthermore, this study provides a potential strategy to maintain the genome stability of industrial strains during fermentation. IMPORTANCE Pol was shown to be critical for cell growth in the yeast Saccharomyces cerevisiae, and deletion of its corresponding gene RAD30 caused a severe growth defect under exposure to oxidative stress with 2 mM H 2 O 2 . Furthermore, we found that Lsm12 physically interacts with Pol and promotes Pol deubiquitination and recruitment. Overall, these findings indicate Lsm12 is a novel regulator mediating Pol deubiquitination that regulates its recruitment in response to DNA damage induced by oxidative stress.

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Chromatin modification and NBS1: their relationship in DNA double-strand break repair

Cited by 14 publications

References 110 publications

NBS1 is regulated by two kind of mechanisms: ATM-dependent complex formation with MRE11 and RAD50, and cell cycle–dependent degradation of protein

NBS1 is regulated by two kind of mechanisms: ATM-dependent complex formation with MRE11 and RAD50, and cell cycle–dependent degradation of protein

Lsm12 mediates Pol·q deubiquitination to help Saccharomyces cerevisiae resist oxidative stress

Lsm12 Mediates Deubiquitination of DNA Polymerase η To Help Saccharomyces cerevisiae Resist Oxidative Stress

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