Maintenance of genome integrity and active homologous recombination in embryonic stem cells

Abstract

Embryonic stem cells (ESCs) possess specific gene expression patterns that confer the ability to proliferate indefinitely and enable pluripotency, which allows ESCs to differentiate into diverse cell types in response to developmental signals. Compared to differentiated cells, ESCs harbor an elevated level of homologous recombination (HR)-related proteins and exhibit exceptional cell cycle control, characterized by a high proliferation rate and a prolonged S phase. HR is involved in several aspects of chromosome maintenance. For instance, HR repairs impaired chromosomes and prevents the collapse of DNA replication forks during cell proliferation. Thus, HR is essential for the maintenance of genomic integrity and prevents cellular dysregulation and lethal events. In addition, abundant HR proteins in the prolonged S phase can efficiently protect ESCs from external damages and protect against genomic instability caused by DNA breaks, facilitating rapid and accurate DNA break repair following chromosome duplication. The maintenance of genome integrity is key to preserving the functions of ESCs and reducing the risks of cancer development, cell cycle arrest, and abnormal replication. Here, we review the fundamental links between the stem cell-specific HR process and DNA damage response as well as the different strategies employed by ESCs to maintain genomic integrity. Embryonic stem cells: extra protection for DNA Embryonic stem cells (ESCs), which give rise to the many specialized cells of the body, have highly effective molecular processes of DNA maintenance and repair which protect their genetic information from damage. Keun Pil Kim and colleagues at Chung-Ang University, Seoul, South Korea, review the strategies found in ESCs to maintain the integrity of their DNA as they develop and multiply. A key feature is the process of homologous recombination (HR) in which one copy of a section of DNA acts as the template allowing a damaged version of the DNA to be repaired. HR also facilitates swapping of sections of DNA when sperm and egg cells form, promoting genetic diversity. HR appears to be especially significant in maintaining ESC DNA as ESCs possess higher levels of key proteins involved in its maintenance and regulation.