Title |
Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms |
Author |
Ji Eun Choi1,2 and Woo-Hyun Chung1,2* |
Address |
1College of Pharmacy, Duksung Women’s University, Seoul 01369, Republic of Korea, 2Innovative Drug Center, Duksung Women’s University, Seoul 01369, Republic of Korea |
Bibliography |
Journal of Microbiology, 58(2),81-91, 2020,
|
DOI |
10.1007/s12275-020-9520-x
|
Key Words |
reactive oxygen species, DNA damage response,
damage checkpoint signaling, genome stability |
Abstract |
The DNA damage checkpoint signaling pathway is a highly
conserved surveillance mechanism that ensures genome integrity
by sequential activation of protein kinase cascades.
In mammals, the main pathway is orchestrated by two central
sensor kinases, ATM and ATR, that are activated in response
to DNA damage and DNA replication stress. Patients
lacking functional ATM or ATR suffer from ataxia-telangiectasia
(A-T) or Seckel syndrome, respectively, with pleiotropic
degenerative phenotypes. In addition to DNA strand
breaks, ATM and ATR also respond to oxidative DNA damage
and reactive oxygen species (ROS), suggesting an unconventional
function as regulators of intracellular redox status.
Here, we summarize the multiple roles of ATM and ATR, and
of their orthologs in Saccharomyces cerevisiae, Tel1 and Mec1,
in DNA damage checkpoint signaling and the oxidative stress
response, and discuss emerging ideas regarding the possible
mechanisms underlying the elaborate crosstalk between those
pathways. This review may provide new insights into the integrated
cellular strategies responsible for maintaining genome
stability in eukaryotes with a focus on the yeast model
organism. |