New insights into the mechanism of RPA in preserving genome stability
Simin Zhang , Xuejie Wang , Han Zhao , Jingyao Shi , Xuefeng Chen
Genome Instability & Disease ›› 2022, Vol. 3 ›› Issue (5) : 255 -266.
New insights into the mechanism of RPA in preserving genome stability
Single-stranded DNA (ssDNA) is a common intermediate produced during normal DNA transactions, including transcription, DNA replication, repair, and recombination. Replication protein A (RPA), an evolutionarily conserved ssDNA-binding protein complex, plays a critical role in these DNA transactions through its dynamic association with ssDNA or proteins. The binding of RPA on ssDNA protects ssDNA from unscheduled nuclease digestion, melts secondary DNA structures, suppresses mutations, and signals the checkpoint for DNA damage or replication stresses. In parallel, RPA serves as a platform for interacting with a number of different proteins to coordinate various DNA metabolic processes. However, our understanding of the regulation and function of RPA is far from complete. Here, we reviewed recent advances on the roles of RPA in regulating replication, repair, nucleosome assembly, rDNA transcription, chromatin epigenetic landscape, and chromosome segregation. In addition, we described the interplay between RPA and the ubiquitin E3 ligase RFWD3 that determines RPA turnover at replication forks or DNA lesion sites. These new findings advance our understanding of the versatile roles of RPA in preserving genome integrity and could provide opportunities to develop therapeutic strategies targeting cancer.
National Natural Science Foundation of China(32070573)
Key Technologies Research and Development Program(2021YFA1100503)
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