CMCB Life Sciences Seminar: Prof. Björn Schumacher, University of Cologne, Institute for Genome Stability in Aging and Disease, CECAD Research Center

Date

May 16, 2024

Time

1:00 PM - 2:00 PM

Speaker

Prof. Björn Schumacher

Affiliation

University of Cologne

Series

CMCB Life Sciences Seminar

Language

en

Main Topic

Willkommen

Other Topics

Willkommen

Description

Hosts: Anna Poetsch (BIOTEC) and Maximina Yun (CRTD)

Title: "Genome Stability in Aging, Inheritance and Disease: New Insights from C. elegans"

Abstract: The demographic change is one of the greatest challenges of our time. Age is the biggest risk factor for a wide range of chronic diseases including dementia, cardiovascular diseases, cancer, and frailty. It is therefore of utmost importance to understand the biology of aging. While the soma ages over the course of an individual’s lifespan, germ cells can be indefinitely perpetuated. 

The genome contains all information for building and maintaining cells, tissues and thus the organism. The DNA is constantly exposed to damage but, in contrast to any other macromolecules, it cannot be replaced but instead requires constant repair. DNA repair mechanisms are thus essential for life and the maintenance of health. DNA repair defects accelerate human aging in rare progeroid syndromes. While the DNA in somatic tissues only needs to be maintained for an individual’s lifespan, germline genomes require indefinite maintenance. We will here discuss new concepts of genome maintenance mechanisms in the germline.

First, we investigated the genome quality control in the germline. We uncovered unexpected transgenerational consequences of DNA damage in paternal genomes. We show that DNA damage in mature sperm leads to structural variants that are generated by maternal Theta-mediated endjoining (TMEJ), which consequently results in genome instability in the progeny. The progeny is incapable to repair the damage due to heterochromatization leading to transgenerational embryonic lethality. Alleviation of the heterochromatization, in contrast, allows access for homologous recombination repair (HRR) thus resolving the genome instability and reversing the transgenerational lethality. We thus uncovered a novel mechanism of the specific consequences of paternal DNA damage and the restrictive repair types fueling genome instability in the consequent generation.

Second, we investigated the mechanisms underlying the limited DNA repair capacities of somatic cells compared to the germline. We found that the DREAM complex represses DNA repair gene expression in somatic cells thus curbing somatic genome maintenance. DREAM inactivation leads to induction of the expression of DNA repair genes in all DNA repair systems consequently enhancing DNA repair kinetics and conferring DNA damage resistance to the soma. We show the DREAM inhibition also in human cells and in mice elevates DNA damage resistance. We propose the DREAM as the first master regulator of somatic DNA repair capacities whose inhibition could augment genome maintenance thus alleviating a fundamental cause of aging.

Links

• Termindetails auf den Webseiten der TU Dresden (https://tu-dresden.de)

Last modified: May 16, 2024, 7:37:56 AM