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

被引：68

作者：

Holmes, J. Bradley ^{[1
,2
]}

Akman, Gokhan ^{[3
]}

Wood, Stuart R. ^{[2
]}

Sakhuja, Kiran ^{[1
]}

Cerritelli, Susana M. ^{[1
]}

Moss, Chloe ^{[3
]}

Bowmaker, Mark R. ^{[3
]}

Jacobs, Howard T. ^{[4
,5
,6
]}

Crouch, Robert J. ^{[1
]}

Holt, Ian J. ^{[3
]}

机构：

[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA

[2] MRC, Mitochondrial Biol Unit, Cambridge CB1 9SY, England

[3] Natl Inst Med Res, MRC, London NW7 1AA, England

[4] Univ Tampere, BioMediTech, FI-33014 Tampere, Finland

[5] Univ Tampere, Tampere Univ Hosp, FI-33014 Tampere, Finland

[6] Univ Helsinki, Res Program Mol Neurol, FI-00014 Helsinki, Finland

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2015年 / 112卷 / 30期

基金：

英国医学研究理事会; 芬兰科学院;

关键词：

DNA replication; RNase H; mitochondrial DNA; replication priming; origin of replication; STRAND SYNTHESIS; RIBONUCLEASE-H; LAGGING-STRAND; ORIGIN; MOUSE; INITIATION; TRANSCRIPTION; MECHANISM; SEQUENCE; MAINTENANCE;

D O I：

10.1073/pnas.1503653112

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：9334 / 9339

页数：6

共 36 条

[1]

Badea TC, 2003, J NEUROSCI, V23, P2314

[2] Revisiting the mouse mitochondrial DNA sequence [J].

Bayona-Bafaluy, MP ;

Acín-Pérez, R ;

Mullikin, JC ;

Park, JS ;

Moreno-Loshuertos, R ;

Hu, PQ ;

Pérez-Martos, A ;

Fernández-Silva, P ;

Bai, YD ;

Enríquez, JA .

NUCLEIC ACIDS RESEARCH, 2003, 31 (18) :5349-5355

[3] Mammalian mitochondrial DNA replicates bidirectionally from an initiation zone [J].

Bowmaker, M ;

Yang, MY ;

Yasukawa, T ;

Reyes, A ;

Jacobs, HT ;

Huberman, JA ;

Holt, IJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (51) :50961-50969

[4] Sodium boric acid: a Tris-free, cooler conductive medium for DNA electrophoresis [J].

Brody, JR ;

Kern, SE .

BIOTECHNIQUES, 2004, 36 (02) :214-+

[5] Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism [J].

Brown, TA ;

Cecconi, C ;

Tkachuk, AN ;

Bustamante, C ;

Clayton, DA .

GENES & DEVELOPMENT, 2005, 19 (20) :2466-2476

[6] ISOLATION AND MAPPING OF A MUTATION IN ESCHERICHIA-COLI WITH ALTERED LEVELS OF RIBONUCLEASE-H [J].

CARL, PL ;

BLOOM, L ;

CROUCH, RJ .

JOURNAL OF BACTERIOLOGY, 1980, 144 (01) :28-35

[7] Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice [J].

Cerritelli, SM ;

Frolova, EG ;

Feng, CG ;

Grinberg, A ;

Love, PE ;

Crouch, RJ .

MOLECULAR CELL, 2003, 11 (03) :807-815

[8] PRIMING OF HUMAN MITOCHONDRIAL-DNA REPLICATION OCCURS AT THE LIGHT-STRAND PROMOTER [J].

CHANG, DD ;

CLAYTON, DA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (02) :351-355

[9] PRECISE IDENTIFICATION OF INDIVIDUAL PROMOTERS FOR TRANSCRIPTION OF EACH STRAND OF HUMAN MITOCHONDRIAL-DNA [J].

CHANG, DD ;

CLAYTON, DA .

CELL, 1984, 36 (03) :635-643

[10] REPLICATION PRIMING AND TRANSCRIPTION INITIATE FROM PRECISELY THE SAME SITE IN MOUSE MITOCHONDRIAL-DNA [J].

CHANG, DD ;

HAUSWIRTH, WW ;

CLAYTON, DA .

EMBO JOURNAL, 1985, 4 (06) :1559-1567

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