Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element

• The majority of mitochondrial DNA replication events are terminated prematurely. The nascent DNA remains stably associated with the template, forming a triple-stranded displacement loop (D-loop) structure. However, the function of the D-loop region of the mitochondrial genome remains poorly understood. Using a comparative genomics approach we here identify two closely related 15 nt sequence motifs of the D-loop, strongly conserved among vertebrates. One motif is at the D-loop 5'-end and is part of the conserved sequence block 1 (CSB1). The other motif, here denoted coreTAS, is at the D-loop 3'-end. Both these sequences may prevent transcription across the D-loop region, since light and heavy strand transcription is terminated at CSB1 and coreTAS, respectively. Interestingly, the replication of the nascent D-loop strand, occurring in a direction opposite to that of heavy strand transcription, is also terminated at coreTAS, suggesting that coreTAS is involved in termination of both transcription and replication. Finally, we demonstrate that the loading of the helicase TWINKLE at coreTAS is reversible, implying that this site is a crucial component of a switch between D-loop formation and full-length mitochondrial DNA replication.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

MOUSE L-CELLS

LIGHT-STRAND PROMOTER

TRANSCRIPTION TERMINATION

POLYMERASE-GAMMA

INITIATION SEQUENCE

PRIMER FORMATION

LAGGING-STRAND

HEAVY-STRAND

RNA

REGION

Biochemistry & Molecular Biology

ANG DD

1985

EMBO JOURNAL

V4

P1559

PPER DP

1981

JOURNAL OF BIOLOGICAL CHEMISTRY

V256

P5109

ANG DD

1984

CELL

V36

P635

ARNES MC

1987

JOURNAL OF BIOLOGICAL CHEMISTRY

V262

P988

ATES OF AMERICA

V107

P16072

ANG DD

1985

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)