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Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.


ABSTRACT: Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to depletion, as the persistent RNA is fully incorporated in mitochondrial DNA. However, the retained primers present an obstacle to the mitochondrial DNA polymerase ? in subsequent rounds of replication and lead to the catastrophic generation of a double-strand break at the origin when the resulting gapped molecules are copied. Hence, the essential role of RNase H1 in mitochondrial DNA replication is the removal of primers at the origin of replication.

SUBMITTER: Holmes JB 

PROVIDER: S-EPMC4522766 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.

Holmes J Bradley JB   Akman Gokhan G   Wood Stuart R SR   Sakhuja Kiran K   Cerritelli Susana M SM   Moss Chloe C   Bowmaker Mark R MR   Jacobs Howard T HT   Crouch Robert J RJ   Holt Ian J IJ  

Proceedings of the National Academy of Sciences of the United States of America 20150710 30


Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to de  ...[more]

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