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.
Highlights
1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; Introduction Embryonic stem cells (ESCs), derived from inner cell mass (ICM), are capable of both self-renewal as well as pluripotency, which is the ability to differentiate into diverse cell types
homologous recombination (HR) processes can be classified into three different subpathways: double-strand breaks (DSBs) repair (DSBR), break-induced replication (BIR), and synthesis-dependent strand annealing (SDSA)
ESCs express higher levels of HR factors than somatic cells. This supports the maintenance of genome integrity, despite the fast cell cycle progression
Summary
Pluripotency by minimizing the induction of differentiation-stimulating signals, while the prolonged S phase permits ESCs to utilize the high-frequency HRbased error-free DNA repair mechanism operating in the S/G2 phase. HR factors bind to DNA strands to prevent additional DNA break resection, which would generate unrepaired ssDNA gaps and facilitate immediate HR-regulated postreplication repair These features strongly suggest that constitutive expression of HR factors plays a crucial role in inhibiting continuous DNA breaks by preventing the accumulation of ssDNA gaps in mESCs, which have a relatively long S phase and rely entirely on genomic integrity during replication. Dmc, the meiosis-specific DNA strand exchange factor, promotes the formation of joint molecules (DNA strand invasion products) between homologous templates in a manner similar to that of RAD5153 It is unknown whether DMC1 and its accessory factors HOP2 and MND1 are expressed in ESCs. HR processes can be classified into three different subpathways: DSB repair (DSBR), break-induced replication (BIR), and synthesis-dependent strand annealing (SDSA).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
