Nondysplastic Ulcerative Colitis Has High Levels of the Homologous Recombination Repair Protein NUCKS1 and Low Levels of the DNA Damage Marker Gamma-H2AX

Background: Helicobacter pylori-induced DNA damage and impaired homologous recombination repair are vital molecular mechanisms for gastric cancer, which mainly count on its virulence factors cytotoxic-associated gene A (CagA) and vacuolating cytotoxin A (VacA). However, the relationship between H. pylori CagA EPIYA motifs and vacA genotypes with DNA damage and homologous recombination repair markers is still not clear. Methods: H. pylori positive and negative gastric biopsies were taken from 165 subjects with different gastric precancerous pathologic stages, and DNA damage marker γH2AX and key homologous recombination repair proteins (CtIP and Rad51) were investigated for their association with H. pylori CagA EPIYA motifs and vacAs-, m-, i-, and d-region genotypes and histology (Sydney classification). Results: Out of 165 patients, 78 were identified as H. pylori-positive. CagA EPIYA motifs were identified as AB, ABC, and ABD in 2 (3.3%), 21 (35%), and 37 (61.7%) patients, respectively, while vacA alleles were identified as: s1, s2, m1, m2, i1, i2, d1, and d2 in 50 (89.3%), 6 (10.7%), 24 (42.9%), 32 (57.1%), 45 (80.4%), 11 (19.6%), 40 (71.4%), and 16 (28.6%) patients, respectively. vacAs1m1i1d1, s1m2i1d1, and s1m2i2d2 were the most prevailing genotypes. γH2AX was highly localized in H. pylori-positive tissues with corresponding CagA EPIYA motifs and vacA genotypes, while Rad51 and CtIP signals were weak. Conclusion: H. pylori were positively correlated with the DNA damage marker in precancerous lesions, but were negatively correlated with the key homologous recombination repair proteins, which may be due to the specific CagA EPIYA motifs and vacA genotypes.

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Biphasic recruitment of TRF2 to DNA damage sites promotes non-sister chromatid homologous recombination repair

Journal of Cell Science ◽

10.1242/jcs.219311 ◽

2018 ◽

Vol 131 (23) ◽

pp. jcs219311 ◽

Cited By ~ 6

Author(s):

Xiangduo Kong ◽

Gladys Mae Saquilabon Cruz ◽

Sally Loyal Trinh ◽

Xu-Dong Zhu ◽

Michael W. Berns ◽

...

Keyword(s):

Dna Damage ◽

Homologous Recombination ◽

Sister Chromatid ◽

Homologous Recombination Repair ◽

Recombination Repair

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Extracellular Signal-Related Kinase Positively Regulates Ataxia Telangiectasia Mutated, Homologous Recombination Repair, and the DNA Damage Response

Cancer Research ◽

10.1158/0008-5472.can-06-2371 ◽

2007 ◽

Vol 67 (3) ◽

pp. 1046-1053 ◽

Cited By ~ 125

Author(s):

Sarah E. Golding ◽

Elizabeth Rosenberg ◽

Steven Neill ◽

Paul Dent ◽

Lawrence F. Povirk ◽

...

Keyword(s):

Dna Damage ◽

Homologous Recombination ◽

Dna Damage Response ◽

Ataxia Telangiectasia ◽

Homologous Recombination Repair ◽

Ataxia Telangiectasia Mutated ◽

Extracellular Signal ◽

Recombination Repair ◽

Damage Response

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PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading

eLife ◽

10.7554/elife.38771 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 17

Author(s):

Gergely Rona ◽

Domenico Roberti ◽

Yandong Yin ◽

Julia K Pagan ◽

Harrison Homer ◽

...

Keyword(s):

Dna Damage ◽

Homologous Recombination ◽

Ubiquitin Ligase ◽

Transcriptional Repression ◽

Genotoxic Stress ◽

Strand Break ◽

Homologous Recombination Repair ◽

Dependent Manner ◽

Ubiquitin Ligase Complex ◽

Recombination Repair

The mammalian FBXL10-RNF68-RNF2 ubiquitin ligase complex (FRRUC) mono-ubiquitylates H2A at Lys119 to repress transcription in unstressed cells. We found that the FRRUC is rapidly and transiently recruited to sites of DNA damage in a PARP1- and TIMELESS-dependent manner to promote mono-ubiquitylation of H2A at Lys119, a local decrease of H2A levels, and an increase of H2A.Z incorporation. Both the FRRUC and H2A.Z promote transcriptional repression, double strand break signaling, and homologous recombination repair (HRR). All these events require both the presence and activity of the FRRUC. Moreover, the FRRUC and its activity are required for the proper recruitment of BMI1-RNF2 and MEL18-RNF2, two other ubiquitin ligases that mono-ubiquitylate Lys119 in H2A upon genotoxic stress. Notably, whereas H2A.Z is not required for H2A mono-ubiquitylation, impairment of the latter results in the inhibition of H2A.Z incorporation. We propose that the recruitment of the FRRUC represents an early and critical regulatory step in HRR.

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Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining

Cells ◽

10.3390/cells9040889 ◽

2020 ◽

Vol 9 (4) ◽

pp. 889 ◽

Cited By ~ 3

Author(s):

Klaudia Szymonowicz ◽

Adam Krysztofiak ◽

Jansje van der Linden ◽

Ajvar Kern ◽

Simon Deycmar ◽

...

Keyword(s):

Dna Damage ◽

Homologous Recombination ◽

Proton Irradiation ◽

Negative Impact ◽

Particle Therapy ◽

Homologous Recombination Repair ◽

End Joining ◽

X Ray ◽

Recombination Repair ◽

Non Homologous End Joining

Technical improvements in clinical radiotherapy for maximizing cytotoxicity to the tumor while limiting negative impact on co-irradiated healthy tissues include the increasing use of particle therapy (e.g., proton therapy) worldwide. Yet potential differences in the biology of DNA damage induction and repair between irradiation with X-ray photons and protons remain elusive. We compared the differences in DNA double strand break (DSB) repair and survival of cells compromised in non-homologous end joining (NHEJ), homologous recombination repair (HRR) or both, after irradiation with an equal dose of X-ray photons, entrance plateau (EP) protons, and mid spread-out Bragg peak (SOBP) protons. We used super-resolution microscopy to investigate potential differences in spatial distribution of DNA damage foci upon irradiation. While DNA damage foci were equally distributed throughout the nucleus after X-ray photon irradiation, we observed more clustered DNA damage foci upon proton irradiation. Furthermore, deficiency in essential NHEJ proteins delayed DNA repair kinetics and sensitized cells to both, X-ray photon and proton irradiation, whereas deficiency in HRR proteins sensitized cells only to proton irradiation. We assume that NHEJ is indispensable for processing DNA DSB independent of the irradiation source, whereas the importance of HRR rises with increasing energy of applied irradiation.

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