Two stages of XRCC1 recruitment and two classes of XRCC1 foci formed in response to low level DNA damage induced by visible light, or stress triggered by heat shock

Utilization of thermal therapy (hyperthermia) is defined as the application of exogenous heat induction and represents a concept that is far from new as it goes back to ancient times when heat was used for treating various diseases, including malignancies. Such therapeutic strategy has gained even more popularity (over the last few decades) since various studies have shed light into understanding hyperthermia's underlying molecular mechanism(s) of action. In general, hyperthermia is applied as complementary (adjuvant) means in therapeutic protocols combining chemotherapy and/or irradiation both of which can induce irreversible cellular DNA damage. Furthermore, according to a number of in vitro, in vivo and clinical studies, hyperthermia has been shown to enhance the beneficial effects of DNA targeting therapeutic strategies by interfering with DNA repair response cascades. Therefore, the continuously growing evidence supporting hyperthermia's beneficial role in cancer treatment can also encourage its application as a DNA repair mitigation strategy. In this review article, we aim to provide detailed information on how hyperthermia acts on DNA damage and repair pathways and thus potentially contributing to various adjuvant therapeutic protocols relevant to more efficient cancer treatment strategies.

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“…inactivation of 8-oxoguanine DNA glycosylase; OGG1) [67] and iii) DNA repair proteins (e.g. induction of XRCC1) [68,69].…”

Section: Base Excision Repair (Ber)mentioning

confidence: 99%

Effects of hyperthermia as a mitigation strategy in DNA damage-based cancer therapies

Mantso

Goussetis

Franco

et al. 2016

Seminars in Cancer Biology

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“…We also cotransfected HeLa cells with vectors encoding fusion proteins: enhanced green fluorescent protein (EGFP)-XRCC1, EGFP-SP100, green fluorescent protein (GFP)-PARP1, EGFP-Lig IIIa or enhanced yellow fluorescent protein (EYFP)-ORC1, and EYFP-ORC5. Two different vectors encoding mRFP-XRCC1 were used as previously described (5). The construct used in preliminary experiments embraced the gene encoding XRCC1 containing 6 point mutations; it was lacking a stop codon, thus resulting in the presence of 23 additional amino acids linked to the protein.…”

Section: Transfection Of Cellsmentioning

confidence: 99%

“…Local DNA damage was induced with focused visible laser light in cells maintained under optimal growth conditions on the stage of Leica TCS SP5 II confocal microscope, as previously described (4,5). Regions of interest (ROI) (2.5 3 2.5 mm or 1 3 6.25 mm, or bleached point) were illuminated with laser line 488 nm (83 mW delivered to the sample) by either scanning ROI several times (6, 10, or 7 scans in Fig.…”

Section: Dna Damage Inductionmentioning

confidence: 99%

“…XRCC1 foci of one subpopulation are located very close to sites of active replication (presumably groups of replication forks). Foci of other group have no adjacent replication region; these foci most likely represent stress bodies formed afar of sites of DNA damage (5). Only some sites of active replication develop SSB and have adjacent XRCC1 focus.…”

Section: Explicit Connectivity Of Novel Xrcc1 Foci To Single-strand Bmentioning

confidence: 99%

“…We have focused our attention on X-ray repair cross-complementing protein 1 (XRCC1). XRCC1 is commonly used as a molecular marker of single-strand DNA breaks (SSBs) because it is recruited rapidly to these lesions and forms distinct repair foci (1)(2)(3)(4)(5). Recruitment of XRCC1 to the sites of DNA damage is promoted by direct interactions with poly(ADP-ribose) (PAR) and the PAR polymerases PARP1 and PARP2 (6)(7)(8).…”

mentioning

confidence: 99%

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PML‐like subnuclear bodies, containing XRCC1, juxtaposed to DNA replication‐based single‐strand breaks

et al. 2018

Self Cite

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DNA lesions induce recruitment and accumulation of various repair factors, resulting in formation of discrete nuclear foci. Using superresolution fluorescence microscopy as well as live cell and quantitative imaging, we demonstrate that X‐ray repair cross‐complementing protein 1 (XRCC1), a key factor in single‐strand break and base excision repair, is recruited into nuclear bodies formed in response to replication‐related single‐strand breaks. Intriguingly, these bodies are assembled immediately in the vicinity of these breaks and never fully colocalize with replication foci. They are structurally organized, containing canonical promyelocytic leukemia (PML) nuclear body protein SP100 concentrated in a peripheral layer, and XRCC1 in the center. They also contain other factors, including PML, poly(ADP‐ribose) polymerase 1 (PARP1), ligase IIIα, and origin recognition complex subunit 5. The breast cancer 1 and ‐2 C terminus domains of XRCC1 are essential for formation of these repair foci. These results reveal that XRCC1‐contaning foci constitute newly recognized PML‐like nuclear bodies that accrete and locally deliver essential factors for repair of single‐strand DNA breaks in replication regions.—Kordon, M. M., Szczurek, A., Berniak, K., Szelest, O., Solarczyk, K., Tworzydlo, M., Wachsmann‐Hogiu, S., Vaahtokari, A., Cremer, C., Pederson, T., Dobrucki, J. W. PML‐like subnuclear bodies, containing XRCC1, juxtaposed to DNA replication‐based single‐strand breaks. FASEB J. 33, 2301–2313 (2019). http://www.fasebj.org

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Amelioration of PM2.5-induced lung toxicity in rats by nutritional supplementation with biochanin A

Xue

Zhang

et al. 2020

Ecotoxicology and Environmental Safety

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Two stages of XRCC1 recruitment and two classes of XRCC1 foci formed in response to low level DNA damage induced by visible light, or stress triggered by heat shock

Cited by 9 publications

References 58 publications

Effects of hyperthermia as a mitigation strategy in DNA damage-based cancer therapies

Effects of hyperthermia as a mitigation strategy in DNA damage-based cancer therapies

PML‐like subnuclear bodies, containing XRCC1, juxtaposed to DNA replication‐based single‐strand breaks

Amelioration of PM2.5-induced lung toxicity in rats by nutritional supplementation with biochanin A

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