Cleavage Factor I Links Transcription Termination to DNA Damage Response and Genome Integrity Maintenance in

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DNA damage occurs constantly in living cells and needs to be recognized and repaired to avoid mutations. DNA repair is particularly relevant for lesions occurring in actively transcribed DNA strands because the RNA polymerase cannot proceed through a damaged site. Stalled RNA polymerases and persisting DNA lesions can lead to genome instability or cell death. Specific mechanisms to repair obstructing DNA lesions are found from bacteria to higher eukaryotes, their malfunction leading to severe genetic syndromes in humans. Termination of transcription comprises cleavage and polyadenylation of the nascent transcript and displacement of the RNA polymerase from its DNA template. These processes, which are crucial for cell viability and growth in eukaryotes, require two major multi-subunit complexes in budding yeast. Here, we found that one of these complexes, Cleavage Factor I (CFI), participates in the cellular response to DNA damage. In addition, we found that CFI dysfunction leads to replication defects, conceivably mediated by stalled RNA polymerases, rendering cell cycle checkpoints mandatory to prevent genomic instability. Our findings emphasize the importance of coordinating transcription termination, DNA damage response and replication in the maintenance of genomic stability suggesting that CFI plays a fundamental function in the coupling of these processes.

Vyšlo v časopise: Cleavage Factor I Links Transcription Termination to DNA Damage Response and Genome Integrity Maintenance in. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004203
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004203

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