Abstract
Environmental agents are constantly challenging cells by damaging DNA, leading to the blockage of transcription elongation. How do cells deal with transcription-blockage and how is transcription restarted after the blocking lesions are removed? Here we review the processes responsible for the removal of transcription-blocking lesions, as well as mechanisms of transcription restart. We also discuss recent data suggesting that blocked RNA polymerases may not resume transcription from the site of the lesion following its removal but, rather, are forced to start over from the beginning of genes.
Highlights
Transcription of DNA-encoded information involves RNA polymerases, which act like molecular motors pulling DNA through their active sites, generating complementary primary RNA molecules.In addition to the initiation step of transcription, RNA synthesis is regulated by the transition into the transcription elongation phase, the rate of elongation and transcription termination [1,2,3,4,5]
To the recovery after ultraviolet light (UV)-irradiation, we found that the recovery of RNA synthesis following camptothecin removal occurred as a wave from the 5'-end of the genes with no recovery detected at the 3'-end of genes [12,118]
Inhibition of transcription is closely linked to the induction of apoptosis so there has been a strong evolutionary pressure to select for factors and processes that resolve these blockages and restore transcription [17,119]
Summary
Transcription of DNA-encoded information involves RNA polymerases, which act like molecular motors pulling DNA through their active sites, generating complementary primary RNA molecules. The primary RNA molecules are spliced into mature forms and exported as RNA-protein complexes to ribosomes in the cytoplasm [6]. Following exposure to DNA-damaging environmental agents, such as ultraviolet light (UV), the elongation process of transcription can be blocked [9,10,11]. Many chemotherapeutic agents, such as DNA topoisomerase I inhibitor camptothecin, can affect the elongation phase of transcription [12,13,14]. We will focus on how DNA damage affects transcription elongation, how cells deal with transcription arrest, and how transcription recovery is accomplished
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