Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Irish Journal of Medical Science (1971 -)
Published in: Irish Journal of Medical Science (1971 -) 3/2011

01-09-2011 | Original Article

Expression of RAD51, BRCA1 and P53 does not correlate with cellular radiosensitivity of normal human fibroblasts

Authors: E. M. Y. Saleh, R. A. E. El-Awady

Published in: Irish Journal of Medical Science (1971 -) | Issue 3/2011

Login to get access

Abstract

Aims

To evaluate the potential role of key DNA repair proteins in the sensitivity of normal human fibroblasts to ionising radiations.

Methods

Radiosensitivity of six human fibroblast strains established from skin biopsies of women who had undergone conservative breast surgery and received a curative breast conserving radiotherapy was measured by colony-formation assay. The expression level of RAD51, BRCA1 and p53 proteins were studied using western blot analysis.

Results

The six fibroblast strains represent a typical spectrum of normal human radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy (SF3.5) ranging from 0.21 to 0.40. We found that these differences in cell survival did not correlate with the expression of RAD51, BRCA1 nor p53 in the tested normal human fibroblast strains.

Conclusions

We conclude that measurement of protein expression of the three tested genes (RAD51, BRCA1 and p53) did not reflect sensitivity of normal fibroblasts to IR.
Literature
1.
Andrei V, Elena A (2003) The role of p53 in the determining sensitivity to radiotherapy. Nature 3:117–129
2.
Leong T, Chao M, Bassal S, McKay M (2003) Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway. Br J Cancer 88:1251–1255PubMedCrossRef
3.
Kasten U, Plottner N, Johansen J, Overgaard J, Dikomey E (1999) Ku70/80 gene expression and DNA-dependent protein kinase (DNA-PK) activity do not correlate with double-strand break (dsb) repair capacity and cellular radiosensitivity in normal human fibroblasts. Br J Cancer 79(7/8):1037–1041PubMedCrossRef
4.
Bentzen S, Overgaard J (1994) Patient to patient variability in the expression of radiation-induced normal tissue injury. Semin Radiat Oncol 4:68–80PubMedCrossRef
5.
Turesson I, Nyman J, Holmberg E, Oden A (1996) Prognostic factors for acute and late skin reactions in radiotherapy patients. Int J Radiat Oncol Biol Phys 36:1065–1075PubMedCrossRef
6.
MaKay M, Peters L (1997) Genetic determinants of radiation response. Report on a symposium held at peter MacCallum Cancer Institute, Melbourne, Australia, 8 August 1996. Int J Radiat Biol 71:225–229CrossRef
7.
Leong T, Whitty J, Keilar M et al (2000) Mutation analysis of BRCA1 and BRCA2 cancer predisposition genes in radiation hypersensitive cancer patients. Int J Radiat Oncol Biol Phys 48:959–965PubMedCrossRef
8.
Severin D, Leong T, Cassidy B et al (2001) Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive cancer patients. Int J Radiat Oncol Biol Phys 50:1323–1331PubMedCrossRef
9.
Sak A, Stueben G, Groneberg M, Böcker W, Stuschke M (2005) Targeting of RAD51-dependent homologous recombination: implications for the radiation sensitivity of human lung cancer cell lines. Br J Cancer 92:1089–1097PubMedCrossRef
10.
Johnson R, Jasin M (2001) Double-strand break-induced homologous recombination in mammalian cells. Biochem Soc Trans 29:196–201PubMedCrossRef
11.
Jasin M (2002) Homologous repair of DNA damage and tumorigenesis: the BRCA connection. Oncogene 21:8981–8993PubMedCrossRef
12.
Thomas L, Luca P, Ashok R, Tom L (2003) Sequence fingerprints in BRCA2 and RAD51: implications for DNA repair and cancer. DNA Repair 2:1015–1028CrossRef
13.
Sonoda E, Takada M, Yamashita Y, Morrison C, Takeda S (2001) Homologous DNA recombination in vertebrate cells. Proc Natl Acad Sci 98(15):8388–8394PubMedCrossRef
14.
Venkitaraman A (2002) Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108(2):171–182PubMedCrossRef
15.
Griffin C, Simpson P, Wilson C, Thacker J (2000) Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nat Cell Biol 2(10):757–761PubMedCrossRef
16.
Takata M, Sasaki M, Sonada E et al (2000) The Rad51 paralog Rad 51B promotes homologous recombinational repair. Mol Cell Biol 20(17):6476–6482PubMedCrossRef
17.
Takata M, Sasaki M, Tachiri S et al (2001) Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Mol Cell Biol 21(8):2858–2866PubMedCrossRef
18.
19.
Connor F, Bertwiste D, Mee P et al (1997) Tumorigenesis and a DNA repair defect in mice with a truncating BRCA2 mutation. Nat Genet 17:423–430PubMedCrossRef
20.
Hakem R, de la Pompa J, Sirard C et al (1996) The tumour suppressor gene BRCA1 is required for embryonic cellular proliferation in the mouse. Cell 85:1009–1023PubMedCrossRef
21.
Suzuki A, de la Pompa J, Hakim R et al (1997) BRCA2 is required for embryonic cellular proliferation in the mouse. Genes Dev 11:1242–1252PubMedCrossRef
22.
Xu X, Qiao W, Linke S et al (2001) Genetic interactions between suppressors BRCA1 and p53 in apoptosis, cell cycle and tumorigenesis. Nat Genet 28:266–271PubMedCrossRef
23.
Henning W, Ellen E, Biao W et al (2000) Dissociation of p53-mediated suppression of homologous recombination from G1/S cell cycle checkpoint control. Oncogene 19:632–639CrossRef
24.
Duddenhöffer C, Rohaly G, Will K, Deppert W, Wiesmüller L (1998) Specific mismatch recognition in heteroduplex intermediates by p53 suggests a role in fidelity control of homologous recombination. Mol Cell Biol 18:5332–5342
25.
Bertrand P, Rouillard D, Boulet A, Vealois C, Soussi T, Lopez B (1997) Increase of spontaneous intrachromosomal homologous recombination in mammalian cells expressing a mutant p53 protein. Oncogene 14:1117–1122PubMedCrossRef
26.
Mekeel K, Tang W, Kachnic Lluo C, Defrank J, Powell S (1997) Inactivation of p53 results in high rates of homologous recombination. Oncogene 14:1847–1857PubMedCrossRef
27.
28.
El-Awady R, Mahmoud M, Saleh E et al (2005) No correlation between radiosensitivity or DSB repair capacity of normal fibroblasts and acute normal tissue reaction after radiotherapy of breast cancer patients. Int J Rad Biol 81(7):501–508PubMedCrossRef
29.
El-Awady R, Dikomey E, Dahm-Daphi J (2003) Radiosensitivity of human tumour cells is correlated with the induction but not with the repair of DNA double-strand breaks. Br J Cancer 89:593–600PubMedCrossRef
30.
31.
Fernet N, Hall J (2004) Genetic biomarkers of therapeutic radiation sensitivity. DNA Repair 3:1237–1243PubMedCrossRef
32.
Sonoda E, Sasaki M, Buerstedde J et al (1998) RAD51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J 17:598–608PubMedCrossRef
33.
Carlomagno F, Burnet N, Turesson I et al (2000) Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities. Int J Cancer 85(6):845–849PubMedCrossRef
34.
Raderschall E, Bazarov A, Cao J et al (2002) Formation of higher-order nuclear RAD51 structures are functionally linked to p21 expression and protection from DNA damage-induced apoptosis. J Cell Sci 115:153–164PubMed
35.
Djuzenova C, Mühl B, Schakowski R, Oppitz U, Flentje M (2004) Normal expression of DNA repair proteins, hMre11, Rad50 and Rad51 but protracted formation of Rad50 containing foci in X-irradiated skin fibroblasts from radiosensitive cancer patients. Br J Cancer 90:2356–2363PubMed
36.
Moynahan M, Cui T, Jasin M (2001) Homology-directed DNA repair, mitomycin-C resistance, and chromosome stability is restored with correction of a BRCA1 mutation. Cancer Res 61:4842–4850PubMed
37.
Li S, Ting N, Zheng L et al (2000) Functional link of BRCA1 and ataxia telangiestasia gene product in DNA damage response. Nature 406:210–215PubMedCrossRef
38.
Wang Y, Cortez D, Yazadi P, Neff N, Elledge S, Qin J (2000) BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev 14:927–939PubMed
39.
Pierce L, Strawderman M, Narod S et al (2000) Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 18:360–3369
40.
41.
Graeber T, Peterson J, Tsai M, Monica K, Fomace A, Giaccia A (1994) Hypoxia induces accumulation of p53 protein, but activation of G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol Cell Biol 14:6264–6277PubMed
42.
Appella E, Anderson C (2001) Post translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 268:2764–2772PubMedCrossRef
43.
Clifford B, Beljin M, Stark G, Taylor W (2003) G2 arrest in response to topoisomerase 11 inhibitors: the role of p53. Cancer Res 63:4074–4081PubMed
44.
Essmann F, Engels I, Totzke G, Schulze-Osthoff K, Jänicke R (2004) Apoptosis resistance of MCF7 breast carcinoma cells to ionizing radiation is independent of p53 and cell cycle control but caused by the lack of caspase-3 and a caffeine-inhibitable events. Cancer Res 64:7065–7072PubMedCrossRef
45.
Böhnke A, Westphal F, Schmidt A, El-Awady R, Dahm-Daphi J (2004) Role of p53 mutations, protein function and DNA damage for the radiosensitivity of human tumour cells. Int J Radiat Biol 80(1):53–63PubMedCrossRef
Metadata
Title
Expression of RAD51, BRCA1 and P53 does not correlate with cellular radiosensitivity of normal human fibroblasts
Authors
E. M. Y. Saleh
R. A. E. El-Awady
Publication date
01-09-2011
Publisher
Springer-Verlag
Published in
Irish Journal of Medical Science (1971 -) / Issue 3/2011
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-010-0554-7

Other articles of this Issue 3/2011

Irish Journal of Medical Science (1971 -) 3/2011 Go to the issue

Case Report

Myopericarditis following Campylobacter infection

Review Article

Aspirin for lower limb arthroplasty thromboprophylaxis: review of international guidelines

Original Article

A five-year review of publication productivity among Irish orthopaedic units

Case Report

The presentation and management of multiple paraganglioma in head and neck

Original Article

The effects of ozone therapy and coenzyme Q10 combination on oxidative stress markers in healthy subjects

Original Article

The incidence and clinical correlates of lithium toxicity: a retrospective review
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits