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 γ 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Holmes JB,Akman G,Wood SR,Sakhuja K,Cerritelli SM,Moss C,Bowmaker MR,Jacobs HT,Crouch RJ,Holt IJdoi
10.1073/pnas.1503653112subject
Has Abstractpub_date
2015-07-28 00:00:00pages
9334-9issue
30eissn
0027-8424issn
1091-6490pii
1503653112journal_volume
112pub_type
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