Abstract
Double-strand breaks in the mitochondrial DNA (mtDNA) result in the formation of linear fragments that are rapidly degraded. However, the identity of the nuclease(s) performing this function is not known. We found that the exonuclease function of the mtDNA polymerase gamma (POLG) is required for this rapid degradation of mtDNA fragments. POLG is recruited to linearized DNA fragments in an origin of replication-independent manner. Moreover, in the absence of POLG exonuclease activity, the prolonged existence of mtDNA linear fragments leads to increased levels of mtDNA deletions, which have been previously identified in the mutator mouse, patients with POLG mutations and normal aging.
Highlights
Double-strand breaks in the mitochondrial DNA result in the formation of linear fragments that are rapidly degraded
We found that polymerase gamma (POLG) minimizes the formation of mitochondrial DNA (mtDNA) deletions by rapidly eliminating linear fragments
For more than 15 years we have known that mtDNA is rapidly eliminated after a DSB6,7,23
Summary
Double-strand breaks in the mitochondrial DNA (mtDNA) result in the formation of linear fragments that are rapidly degraded. The mtDNA mutator mice, which harbor an exonuclease/proofreading inactive catalytic subunit of the mtDNA polymerase gamma (PolgD257A/D257A), showed the presence of an 11 kb linear mtDNA fragment which corresponds to most of the mtDNA major arc (the longer DNA region between origins of heavy (OH) and light (OL) strand replication)[11] These mice have an increased rate of mtDNA point mutation formation and, more importantly, an accumulation of multiple large deletions which were suggested to be the driving force behind their premature aging phenotype[11,12,13]. We found that POLG minimizes the formation of mtDNA deletions by rapidly eliminating linear fragments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
