Homologous recombination-mediated repair of DNA double-strand breaks operates in mammalian mitochondria

Dahal, Sumedha and Dubey, Shubham and Raghavan, Sathees C (2018) Homologous recombination-mediated repair of DNA double-strand breaks operates in mammalian mitochondria. In: CELLULAR AND MOLECULAR LIFE SCIENCES, 75 (9). pp. 1641-1655.

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Abstract

Mitochondrial DNA is frequently exposed to oxidative damage, as compared to nuclear DNA. Previously, we have shown that while microhomology-mediated end joining can account for DNA deletions in mitochondria, classical nonhomologous DNA end joining, the predominant double-strand break (DSB) repair pathway in nucleus, is undetectable. In the present study, we investigated the presence of homologous recombination (HR) in mitochondria to maintain its genomic integrity. Biochemical studies revealed that HR-mediated repair of DSBs is more efficient in the mitochondria of testes as compared to that of brain, kidney and spleen. Interestingly, a significant increase in the efficiency of HR was observed when a DSB was introduced. Analyses of the clones suggest that most of the recombinants were generated through reciprocal exchange, while similar to 30% of recombinants were due to gene conversion in testicular extracts. Colocalization and immunoblotting studies showed the presence of RAD51 and MRN complex proteins in the mitochondria and immunodepletion of MRE11, RAD51 or NIBRIN suppressed the HR-mediated repair. Thus, our results reveal importance of homologous recombination in the maintenance of mitochondrial genome stability.

Item Type:	Journal Article
Publication:	CELLULAR AND MOLECULAR LIFE SCIENCES
Publisher:	SPRINGER BASEL AG, PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
Additional Information:	Copy right for this article belong to SPRINGER BASEL AG, PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	04 May 2018 18:49
Last Modified:	04 May 2018 18:49
URI:	http://eprints.iisc.ac.in/id/eprint/59692

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