Efficiency of nonhomologous DNA end joining varies among somatic tissues,despite similarity in mechanism |
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Authors: | Sheetal Sharma Bibha Choudhary Sathees C Raghavan |
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Institution: | (1) Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India;(2) Manipal Institute of Regenerative Medicine, Manipal University, Bangalore, 560 071, India; |
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Abstract: | Failure to repair DNA double-strand breaks (DSBs) can lead to cell death or cancer. Although nonhomologous end joining (NHEJ)
has been studied extensively in mammals, little is known about it in primary tissues. Using oligomeric DNA mimicking endogenous
DSBs, NHEJ in cell-free extracts of rat tissues were studied. Results show that efficiency of NHEJ is highest in lungs compared
to other somatic tissues. DSBs with compatible and blunt ends joined without modifications, while noncompatible ends joined
with minimal alterations in lungs and testes. Thymus exhibited elevated joining, followed by brain and spleen, which could
be correlated with NHEJ gene expression. However, NHEJ efficiency was poor in terminally differentiated organs like heart,
kidney and liver. Strikingly, NHEJ junctions from these tissues also showed extensive deletions and insertions. Hence, for
the first time, we show that despite mode of joining being generally comparable, efficiency of NHEJ varies among primary tissues
of mammals. |
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