![]() ![]() The Y-family DNA polymerase κ (pol κ) functions in mammalian nucleotide-excision repair. Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. Transcription-coupled DNA repair: two decades of progress and surprises. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. A METT元–METTL14 complex mediates mammalian nuclear RNA N 6-adenosine methylation. Thus, we have uncovered a novel function for RNA m 6A modification in the ultraviolet-induced DNA damage response, and our findings collectively support a model in which m 6A RNA serves as a beacon for the selective, rapid recruitment of Pol κ to damage sites to facilitate repair and cell survival. Importantly, Pol κ overexpression qualitatively suppressed the cyclobutane pyrimidine removal defect associated with METT元 loss. DNA polymerase κ (Pol κ), which has been implicated in both nucleotide excision repair and trans-lesion synthesis 5, 6, required the catalytic activity of METT元 for immediate localization to ultraviolet-induced DNA damage sites. Multiple DNA polymerases are involved in the ultraviolet response, some of which resynthesize DNA after the lesion has been excised by the nucleotide excision repair pathway 3, while others participate in trans-lesion synthesis to allow replication past damaged lesions in S phase 4. In the absence of METT元 catalytic activity, cells showed delayed repair of ultraviolet-induced cyclobutane pyrimidine adducts and elevated sensitivity to ultraviolet, demonstrating the importance of m 6A in the ultraviolet-responsive DNA damage response. This modification occurs on numerous poly(A) + transcripts and is regulated by the methyltransferase METT元 (methyltransferase-like 3) 1 and the demethylase FTO (fat mass and obesity-associated protein) 2. Here we report that methylation at the 6 position of adenosine (m 6A) in RNA is rapidly (within 2 min) and transiently induced at DNA damage sites in response to ultraviolet irradiation. A system of DNA repair, called the DNA damage response, detects and repairs damaged DNA and prevents cell division until the repair is complete. Cell proliferation and survival require the faithful maintenance and propagation of genetic information, which are threatened by the ubiquitous sources of DNA damage present intracellularly and in the external environment. ![]()
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