Abstract
Monocytes, which play a crucial role in the immune system, are characterized by an enormous sensitivity to oxidative stress. As they lack four key proteins responsible for DNA damage response (DDR) pathways, they are especially prone to reactive oxygen species (ROS) exposure leading to oxidative DNA lesions and, consequently, ROS-driven apoptosis. Although such a phenomenon is of important biological significance in the regulation of monocyte/macrophage/dendritic cells’ balance, it also a challenge for monocytic mechanisms that have to provide and maintain genetic stability of its own DNA. Interestingly, apurinic/apyrimidinic endonuclease 1 (APE1), which is one of the key proteins in two DDR mechanisms, base excision repair (BER) and non-homologous end joining (NHEJ) pathways, operates in monocytic cells, although both BER and NHEJ are impaired in these cells. Thus, on the one hand, APE1 endonucleolytic activity leads to enhanced levels of both single- and double-strand DNA breaks (SSDs and DSBs, respectively) in monocytic DNA that remain unrepaired because of the impaired BER and NHEJ. On the other hand, there is some experimental evidence suggesting that APE1 is a crucial player in monocytic genome maintenance and stability through different molecular mechanisms, including induction of cytoprotective and antioxidant genes. Here, the dual face of APE1 is discussed.
Highlights
Monocytes (MOs) are mononuclear phagocytic cells that are mostly produced in bone marrow and released into the bloodstream
AP endonuclease is well-know base excision repair (BER) protein, monocytes’ repair pathways are impaired, which is why we present a perspective on future research
We focused mainly on the known roles of apyrimidinic endonuclease 1 (APE1), through which it can act as a kind of ‘backup system’, modulating the genetic stability in monocytes
Summary
Monocytes (MOs) are mononuclear phagocytic cells that are mostly produced in bone marrow and released into the bloodstream. In response to chemokines and cytokines, they are able to cross the walls of blood vessels, migrate to tissue, and differentiate into either dendritic cells (DCs) or macrophages (MAs). They are called ‘the first line of defense’ because they take part in defending the host against infections, remove the infection agents by gobbling up the invading pathogens, and present antigens to lymphocytes in the immune resistance process. Monocytes are involved in regenerating and maintaining the tissue homeostasis They are engaged in both pro- and anti-inflammatory processes because of their ability to produce a wide range of cytokines that promote or inhibit inflammation, respectively. A deeper understanding of the molecular basis of some diseases might be pivotal for the development of therapy interventions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
