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Imprecision and DNA break repair biased towards incompatible end joining in leukemia
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Gassner, Franz, Schubert, Maria, Rebhandl, Stefan, Spandl, Karina, Zaborsky, Nadja, Catakovic, Kemal, Blaimer, Stephanie, Hebenstreit, Daniel, Griel, Richard and Geisberger, Roland (2017) Imprecision and DNA break repair biased towards incompatible end joining in leukemia. Molecular Cancer Research, 16 (3). pp. 428-438. doi:10.1158/1541-7786 ISSN 1541-7786.
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Official URL: http://doi.org/10.1158/1541-7786
Abstract
Cancer is a genetic disease caused by mutations and chromosomal abnormalities that contribute to uncontrolled cell growth. In addition, cancer cells can rapidly respond to conventional and targeted therapies by accumulating novel and often specific genetic lesions leading to acquired drug resistance and relapsing disease. In chronic lymphocytic leukemia (CLL), however, diverse chromosomal aberrations often occur. In many cases, improper repair of DNA double-strand breaks (DSB) is a major source for genomic abnormalities. Therefore, this study examined the repair of DNA DSBs by nonhomologous end joining (NHEJ) in CLL by performing plasmid-based repair assays in primary CLL cells and normal B cells, isolated from patients, as well as TALEN/Cas9–induced chromosomal deletions in the CLL cell line Mec1. It is demonstrated that DNA repair is aberrant in CLL cells, featuring perturbed DNA break structure preference with efficient joining of noncohesive ends and more deletions at repair junctions. In addition, increased microhomology-mediated end joining (MMEJ) of DNA substrates was observed in CLL together with increased expression of MMEJ-specific repair factors. In summary, these data identify major differences in DNA repair efficiency between CLL cells and normal B cells isolated from patients.
| Item Type: | Journal Article | |||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Chronic lymphocytic leukemia , Chronic lymphocytic leukemia--Treatment, DNA, DNA repair | |||||||||||||||||||||
| Journal or Publication Title: | Molecular Cancer Research | |||||||||||||||||||||
| Publisher: | American Association for Cancer Research | |||||||||||||||||||||
| ISSN: | 1541-7786 | |||||||||||||||||||||
| Official Date: | 8 December 2017 | |||||||||||||||||||||
| Dates: |
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| Volume: | 16 | |||||||||||||||||||||
| Number: | 3 | |||||||||||||||||||||
| Page Range: | pp. 428-438 | |||||||||||||||||||||
| DOI: | 10.1158/1541-7786 | |||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||
| Date of first compliant deposit: | 1 November 2017 | |||||||||||||||||||||
| Date of first compliant Open Access: | 29 January 2018 | |||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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