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

Kordon, Magdalena; Szczurek, Aleksander; Berniak, Krzysztof; Szelest, Oskar; Solarczyk, Kamil; Tworzydło, Magdalena; Wachsmann‐Hogiu, Sebastian; Vaahtokari, Anne; Cremer, Christoph; Pederson, Thoru; Dobrucki, Jurek

doi:10.1096/fj.201801379r

Cited by 10 publications

(7 citation statements)

References 57 publications

(84 reference statements)

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“…As an alternative to detecting DNA lesions directly, dedicated DNA repair factors or specific post-translational modifications, detected via fluorescence microscopy, are widely used as sensitive damage reporters. Accordingly, localization of a core SSB repair factor, XRCC1, has allowed for monitoring SSBs [27][28][29][30][31]. Obvious limitations to this approach are common problems associated with chromatin accessibility and the staining procedure, a dependence on the repair process itself, a possible accumulation of DNA damage makers at nondamaged sites [32,33], and the uncertainty of how well the position and intensity of a repair focus correlate to the properties and number of the causative lesion(s) [29,34].…”

Section: 'Classical' Methods To Detect and Quantify Ssbsmentioning

confidence: 99%

Exploring the SSBreakome: genome‐wide mapping of DNA single‐strand breaks by next‐generation sequencing

Zilio

Ulrich

2020

The FEBS Journal

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Mapping the genome-wide distribution of DNA lesions is key to understanding damage signalling and DNA repair in the context of genome and chromatin structure. Analytical tools based on high-throughput next-generation sequencing have revolutionized our progress with such investigations, and numerous methods are now available for various base lesions and modifications as well as for DNA double-strand breaks. Considering that single-strand breaks are by far the most common type of lesion and arise not only from exposure to exogenous DNA-damaging agents, but also as obligatory intermediates of DNA replication, recombination and repair, it is surprising that our insight into their genome-wide patterns, that is the 'SSBreakome', has remained rather obscure until recently, due to a lack of suitable mapping technology. Here we briefly review classical methods for analysing single-strand breaks and discuss and compare in detail a series of recently developed high-resolution approaches for the genome-wide mapping of these lesions, their advantages and limitations and how they have already provided valuable insight into the impact of this type of damage on the genome.

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Section: 'Classical' Methods To Detect and Quantify Ssbsmentioning

confidence: 99%

Exploring the SSBreakome: genome‐wide mapping of DNA single‐strand breaks by next‐generation sequencing

Zilio

Ulrich

2020

The FEBS Journal

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“…He proposed that the DNA repair protein XRCC1 forms PML-like foci in close proximity to the replication-associated SSBs. These foci contain other proteins involved in DNA damage repair, including PARP1 and 53BP1, possibly providing essential factors for the repair process [10]. The importance of colloid-like foci for DNA repair was also highlighted in the work presented by Olga Lavrik (Novosibirsk State University, Russia), who showed that poly(ADP-ribose) polymerase (PARP) catalyzes these polymers (PAR) at double-stranded DNA breaks.…”

Section: Single-molecule Visualizationmentioning

confidence: 97%

The cell nucleus. A study in Burgundy

Demidov

Aksenova

Dasso

et al. 2019

Nucleus

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Wilhelm Bernhard's revolutionary microscopy techniques helped him put forward the hypothesis of specialized compartmentalization of the nucleus. He also described for the first time the nuclear bodies and peri-chromatin fibrils, and demonstrated that these granules contain an RNA component. The tradition of biennial workshops, named after this great scientist, continues, and this year it took place in the heart of Burgundy, in Dijon, France (May 20-24, 2019, organized by INSERM UMR1231, UBFC), where well-fed participants emphasized the importance of viewing the cell nucleus as a hub of specialized colloidal compartments that orchestrate replication, transcription and nuclear transport.

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“…5 In recent decades, substantial evidence has shown that the ORC is involved in other biological processes and conditions, such as heterochromatin formation, cytokinesis, viral replication, DNA damage repair, cognitive impairment, and radiation inflammatory response. [6][7][8][9][10][11] ORC genes are also known to be differentially expressed in a number of tumors, such as gliomas, 12 endometrial cancer, 13 colon cancer, [14][15][16] gastric cancer, 17,18 liver cancer, 19 esophageal cancer, 20 and lung cancer. 21 They are implicated in diverse biological processes, including cell proliferation, migration, invasion, and chemotherapy resistance.…”

Section: Introductionmentioning

confidence: 99%

Expression and Clinical Significance of Origin Recognition Complex Subunit 6 in Breast Cancer – A Comprehensive Bioinformatics Analysis

Chen¹,

Jin²,

Xin³

et al. 2021

IJGM

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Objective We aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC). Methods Kaplan–Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan–Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC. Results ORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration. Conclusion ORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.

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

Cited by 10 publications

References 57 publications

Exploring the SSBreakome: genome‐wide mapping of DNA single‐strand breaks by next‐generation sequencing

Exploring the SSBreakome: genome‐wide mapping of DNA single‐strand breaks by next‐generation sequencing

The cell nucleus. A study in Burgundy

Expression and Clinical Significance of Origin Recognition Complex Subunit 6 in Breast Cancer – A Comprehensive Bioinformatics Analysis

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