Am J Blood Res 2011;1(1):1-12
Original Article
Premature transcript termination, trans-splicing and DNA repair: a vicious path
to cancer
Eric Kowarz, Jennifer Merkens, Michael Karas,Theo Dingermann, Rolf Marschalek
Institute of Pharmaceutical Biology / DCAL / ZAFES / CEF, JWG-University of Frankfurt, Biocenter, Max-von-Laue-Str. 9, D-
60438 Frankfurt/Main, Germany; Institute of Pharmaceutical Chemistry / ZAFES / CEF, JWG-University of Frankfurt, Biocenter,
Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
Received March 14, 2011; accepted April 4, 2011; Epub April 7, 2011; published June 15, 2011
Abstract: So far, about 800 different chromosomal translocations have been characterized in hemato-malignant and solid
tumors. Chromosomal translocations mostly result in the expression of chimeric fusion proteins associated with enhanced
proliferation and/or malignant transformation. Here, we demonstrate that genes frequently involved in such genetic
rearrangements exhibit a unique feature: premature transcriptional termination. These early-terminated RNA molecules have
an abundance of 10-20% when compared to their cognate full-length transcripts. They exhibit an unsaturated splice donor site
that gives rise to trans-splicing events, leading to RNAs displaying exon repetitions or chimeric fusion RNAs. These arbitrary
fusion RNAs mimic the presence of a chromosomal translocation in genetically unaffected cells. Based on our and published
data, we propose the hypothesis that these artificial “chimeric fusion transcripts” may influence DNA repair processes,
resulting in the generation of de novo chromosomal translocations. This idea provides a rational explanation why different
individuals suffer from nearly identical genetic rearrangements. (AJBR1103001).
Keywords: Acute leukemia, chromosomal translocations, early-terminated transcripts, transsplicing, DNA repair, RNA-
templated DNA repair
Full Text PDF
Address all correspondence to:
Dr. Rolf Marschalek
Institute of Pharmaceutical Biology
JWG-University Frankfurt
Biocenter, N230, 3.03
Max-von-Laue-Str. 9
D-60438 Frankfurt/Main
Tel: +49-69-798-29647
Fax: +49-69-798-29662
E-mail: rolf.marschalek@em.uni-frankfurt.de
Original Article
Premature transcript termination, trans-splicing and DNA repair: a vicious path
to cancer
Eric Kowarz, Jennifer Merkens, Michael Karas,Theo Dingermann, Rolf Marschalek
Institute of Pharmaceutical Biology / DCAL / ZAFES / CEF, JWG-University of Frankfurt, Biocenter, Max-von-Laue-Str. 9, D-
60438 Frankfurt/Main, Germany; Institute of Pharmaceutical Chemistry / ZAFES / CEF, JWG-University of Frankfurt, Biocenter,
Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
Received March 14, 2011; accepted April 4, 2011; Epub April 7, 2011; published June 15, 2011
Abstract: So far, about 800 different chromosomal translocations have been characterized in hemato-malignant and solid
tumors. Chromosomal translocations mostly result in the expression of chimeric fusion proteins associated with enhanced
proliferation and/or malignant transformation. Here, we demonstrate that genes frequently involved in such genetic
rearrangements exhibit a unique feature: premature transcriptional termination. These early-terminated RNA molecules have
an abundance of 10-20% when compared to their cognate full-length transcripts. They exhibit an unsaturated splice donor site
that gives rise to trans-splicing events, leading to RNAs displaying exon repetitions or chimeric fusion RNAs. These arbitrary
fusion RNAs mimic the presence of a chromosomal translocation in genetically unaffected cells. Based on our and published
data, we propose the hypothesis that these artificial “chimeric fusion transcripts” may influence DNA repair processes,
resulting in the generation of de novo chromosomal translocations. This idea provides a rational explanation why different
individuals suffer from nearly identical genetic rearrangements. (AJBR1103001).
Keywords: Acute leukemia, chromosomal translocations, early-terminated transcripts, transsplicing, DNA repair, RNA-
templated DNA repair
Full Text PDF
Address all correspondence to:
Dr. Rolf Marschalek
Institute of Pharmaceutical Biology
JWG-University Frankfurt
Biocenter, N230, 3.03
Max-von-Laue-Str. 9
D-60438 Frankfurt/Main
Tel: +49-69-798-29647
Fax: +49-69-798-29662
E-mail: rolf.marschalek@em.uni-frankfurt.de
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