Role of p38 in replication of Trypanosoma brucei kinetoplast DNA |
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Authors: | Liu Beiyu Molina Henrik Kalume Dario Pandey Akhilesh Griffith Jack D Englund Paul T |
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Institution: | Department of Biological Chemistry, Johns Hopkins Medical School, 725 N. Wolfe St., Baltimore, MD 21205, USA. |
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Abstract: | Trypanosomes have an unusual mitochondrial genome, called kinetoplast DNA, that is a giant network containing thousands of interlocked minicircles. During kinetoplast DNA synthesis, minicircles are released from the network for replication as theta-structures, and then the free minicircle progeny reattach to the network. We report that a mitochondrial protein, which we term p38, functions in kinetoplast DNA replication. RNA interference (RNAi) of p38 resulted in loss of kinetoplast DNA and accumulation of a novel free minicircle species named fraction S. Fraction S minicircles are so underwound that on isolation they become highly negatively supertwisted and develop a region of Z-DNA. p38 binds to minicircle sequences within the replication origin. We conclude that cells with RNAi-induced loss of p38 cannot initiate minicircle replication, although they can extensively unwind free minicircles. |
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