hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress

Paquet, Nicolas; Adams, Mark N.; Ashton, Nicholas W.; Touma, Christine; Gamsjaeger, Roland; Cubeddu, Liza; Leong, Vincent; Beard, Sam; Bolderson, Emma; Botting, Catherine H.; O’Byrne, Kenneth J.; Richard, Derek J.

doi:10.1038/srep27446

Cited by 33 publications

(62 citation statements)

References 44 publications

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“…However, this model is not compatible with the disulphide-mediated hSSB1 tetramer assembled under oxidized conditions (Touma et al, 2017). In line with this notion, tetramerization of hSSB1 has been shown to be dispensable for DSB repair (Paquet et al, 2016).…”

Section: Recognition Of Ssdnamentioning

confidence: 88%

“…hSSB1 is a monomer under reducing conditions (Richard et al, 2008;Richard et al, 2009). However, oxidation stress can promote hSSB1 to form a tetramer, involved in oxidative DNA damage repair and is similar to other tetrameric SSBs (Paquet et al, 2016;Touma et al, 2017). The tetrameric SSBs from E. coli (Ec-SSB) and P. falciparum (Pf-SSB) consist of two distinct dimer interfaces, an extensive interface formed by subunits I and II (or subunits III and IV) with a buried surface area of 1200 Å 2 and a significantly smaller interface formed by subunits II and III (or subunits I and IV) with a buried surface area of 600 Å 2 (Antony et al, 2012;Raghunathan et al, 2000).…”

Section: Recognition Of Ssdnamentioning

confidence: 99%

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Crystal Structure of INTS3/INTS6 complex reveals Functional Importance of INTS3 dimerization in DSB Repair

Cheng

Bharath

et al. 2020

Preprint

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SOSS1 is a single-stranded DNA (ssDNA)-binding protein complex that plays a critical role in double-strand DNA break (DSB) repair. SOSS1 consists of three subunits: INTS3, SOSSC, and hSSB1 with INTS3 serving as a scaffold to stabilize this complex. Moreover, the integrator complex subunit 6 (INTS6) participates in the DNA damage response through direct binding to INTS3 but how INTS3 interacts with INTS6 thereby, impacting DBS repair is not clear.Here, we determined the crystal structure of the C-terminus of INTS3 (INTS3c) in complex with the C-terminus of INTS6 (INTS6c) at a resolution of 2.4 Å. Structure analysis revealed that two INTS3c subunits dimerize and interact with INTS6c via conserved residues. Subsequent biochemical analyses confirmed that INTS3c forms a stable dimer and INTS3 dimerization is important for recognizing the longer ssDNA. Perturbation of INTS3c dimerization and disruption of the INTS3c/INTS6c interaction, impair the DSB repair process. Altogether, these results unravel the underappreciated role of INTS3 dimerization and the molecular basis of INTS3/INTS6 interaction in DSB repair.

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Section: Recognition Of Ssdnamentioning

confidence: 88%

Section: Recognition Of Ssdnamentioning

confidence: 99%

Crystal Structure of INTS3/INTS6 complex reveals Functional Importance of INTS3 dimerization in DSB Repair

Cheng

Bharath

et al. 2020

Preprint

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“…In response to DNA damage caused by oxidative stress in mitochondria, SSBP1 is an essential protein. 23) Furthermore, SSBP1 mRNA and protein expres-sion was down-regulated by Ang II and restored by valsartan treatment ( Figure 2G-I). These results indicated the disruption of mitochondrial function by Ang II in the mouse heart.…”

Section: Ang II Infusion Causes Cardiac Fibrosis In Micementioning

confidence: 92%

Single-Stranded DNA-Binding Protein 1 Abrogates Cardiac Fibroblast Proliferation and Collagen Expression Induced by Angiotensin II

Tian

Sun²,

et al. 2018

Int. Heart J.

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Angiotensin II (Ang II), an effective component of renin-angiotensin system, plays a pivotal role in cardiac fibrosis, which may further contribute to heart failure. Single-stranded DNA-binding protein 1 (SSBP1), a DNA damage response protein, regulates both mitochondrial function and extracellular matrix remodeling. In this study, we aim to investigate the role of SSBP1 in cardiac fibrosis that is induced by Ang II. We infused C57BL/ 6J mice with vehicle or Ang II and valsartan using implanted osmotic mini-pumps. Moreover, heart function was examined by echocardiography and cardiac fibrosis was analyzed via picrosirus red staining. The expression of COL1A1, COL3A1, SSBP1, p53, Nox1, and Nox4 was analyzed via qRT-PCR and/or immunoblots. The SSBP1 expression was manipulated via SSBP1 shRNA and pcDNA3.1/SSBP1 plasmids, while the p53 expression was enhanced via AdCMV-p53 infection. The exposure to Ang II increased the mouse heart weight, systolic blood pressure, interventricular septal thickness diastolic (IVSTD) and left ventricular end posterior wall dimension diastolic (LVPWD), which were counteracted by valsartan. While cardiac fibrosis was induced with Ang II treatment, it was relieved using valsartan. Furthermore, Ang II treatment caused mitochondrial dysfunction, oxidative stress, and down-regulated SSBP1 expression. The knockdown of SSBP1 increased cardiac fibroblast proliferation, collagen expression, and decreased p53 expression, which was impeded via SSBP1 overexpression. Moreover, the forced expression of p53 abated the fibroblast proliferation and collagen expression that was induced by Ang II. To summarize, SSBP1 was down-regulated by Ang II and implicated in cardiac fibroblast proliferation and collagen expression partly via the p53 protein.

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“…Here, hSSB1 has been reported to stimulate resection of double-strand DNA break ends by the Mre11-Nbs1-Rad50 (MRN) [22, 23] and Exo1 [24] nucleases, as well as activation of the ATM kinase [20]. Additional roles for hSSB1 have also been reported in the response to replication fork stalling [21, 25], as well as in oxidative stress repair [26, 27]. …”

Section: Introductionmentioning

confidence: 99%

Novel insight into the composition of human single-stranded DNA-binding protein 1 (hSSB1)-containing protein complexes

et al. 2016

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BackgroundSingle-stranded DNA-binding proteins are essential cellular components required for the protection, metabolism and processing of single-stranded DNA. Human single-stranded DNA-binding protein 1 (hSSB1) is one such protein, with described roles in genome stability maintenance and transcriptional regulation. As yet, however, the mechanisms through which hSSB1 functions and the binding partners with which it interacts remain poorly understood.ResultsIn this work, hSSB1 was immunoprecipitated from cell lysate samples that had been enriched for non-soluble nuclear proteins and those associating with hSSB1 identified by mass spectrometry. In doing so, 334 potential hSSB1-associating proteins were identified, with known roles in a range of distinct biological processes. Unexpectedly, whilst hSSB1 has largely been studied in a genome stability context, few other DNA repair or replication proteins were detected. By contrast, a large number of proteins were identified with roles in mRNA metabolism, reflecting a currently emerging area of hSSB1 study. In addition, numerous proteins were detected that comprise various chromatin-remodelling complexes.ConclusionsThese findings provide new insight into the binding partners of hSSB1 and will likely function as a platform for future research.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-016-0077-5) contains supplementary material, which is available to authorized users.

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hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress

Cited by 33 publications

References 44 publications

Crystal Structure of INTS3/INTS6 complex reveals Functional Importance of INTS3 dimerization in DSB Repair

Crystal Structure of INTS3/INTS6 complex reveals Functional Importance of INTS3 dimerization in DSB Repair

Single-Stranded DNA-Binding Protein 1 Abrogates Cardiac Fibroblast Proliferation and Collagen Expression Induced by Angiotensin II

Novel insight into the composition of human single-stranded DNA-binding protein 1 (hSSB1)-containing protein complexes

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