Both heavy strand replication origins are active in partially duplicated human mitochondrial DNAs.

Abstract:

:The replication of human mitochondrial DNA (mtDNA) is initiated from a pair of displaced origins, one priming continuous synthesis of daughter-strand DNA from the heavy strand (OH) and the other priming continuous synthesis from the light strand (OL). In patients with sporadic large-scale rearrangements of mitochondrial DNA (i.e., partially-deleted [Delta-mtDNA] and partially-duplicated [dup-mtDNA] molecules), the dup-mtDNAs typically contain extra origins of replication, but it is unknown at present whether they are competent for initiation of replication. Using cybrids harboring each of two types of dup-mtDNAs-one containing two OHs and two OLs, and one containing two OHs and one OL-we used ligation-mediated polymerase chain reaction (LMPCR) to measure the presence and relative amounts of nascent heavy strands originating from each OH. We found that the nascent heavy strands originated almost equally from the two OHs in each cell line, indicating that the extra OH present on a partially duplicated mtDNA is competent for heavy strand synthesis. This extra OH could potentially confer a replicative advantage to dup-mtDNAs, as these molecules may have twice as many opportunities to initiate replication compared to wild-type (or partially deleted) molecules.

authors

Umeda S,Tang Y,Okamoto M,Hamasaki N,Schon EA,Kang D

doi

10.1006/bbrc.2001.5436

subject

Has Abstract

pub_date

2001-08-31 00:00:00

pages

681-7

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(01)95436-1

journal_volume

286

pub_type

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