The Centre of New Technologies invites to a seminar by
Michał Szymański, PhD
Intercollegiate Faculty of Biotechnology of the University of Gdansk and Medical University of Gdańsk
Title: An interplay between DNA replication and repair in human mitochondria
Date: January 31st, 2020 at 12 p.m.
Venue: Centre of New Technologies, Banacha 2C,
Lecture Hall 0142 (Ground floor)
Host: prof. Agnieszka Chacińska
Human mitochondrial DNA (mtDNA) replication is initiated from two different origins of replication, OriH and OriL where mitochondrial RNA polymerase (POLRMT) initiates the synthesis of short RNA primers. These primers are then used by human mitochondrial DNA polymerase γ (Polγ) to initiate DNA synthesis. Once initiated, both H-strand and L-strand synthesis proceed continuously until two new daughter molecules are formed. The RNA primers at the 5′-ends of the nascent strands must be removed by nucleases and replaced by DNA. Failure to remove ribonucleotides from mtDNA may impair ligation and DNA synthesis, causing DNA lesions which during subsequent replication cycles can cause double-strand mtDNA breaks and deletions. Number of nucleases have been implicated in primer removal but they either lack necessary enzymatic activity or their mitochondrial localization is under debate. Thus, the molecular mechanism RNA primer removal and subsequent termination of DNA replication in human mitochondria is not well understood. I will demonstrate that human mitochondrial nuclease, crucial for mitochondrial DNA repair, is efficient in removal of RNA primers and in concert with other mitochondrial factors promotes processing and termination of mtDNA replication.
