A UV-responsive internal ribosome entry site enhances serine hydroxymethyltransferase 1 expression for DNA damage repair.
Thymidine nucleotides are required for faithful DNA synthesis and repair, and their de novo biosynthesis is regulated by serine hydroxymethyltransferase 1 (SHMT1). The SHMT1 transcript contains a heavy chain ferritin, heterogeneous nuclear ribonucleoprotein H2, and CUG-binding protein 1-responsive internal ribosome entry site (IRES) that regulates SHMT1 translation. In this study a non-lethal dose of UVC is shown to increase SHMT1 IRES activity and protein levels in four different cell lines. The mechanism for the UV-induced activation of the SHMT1 IRES involves an increase in heavy chain ferritin and heterogeneous nuclear ribonucleoprotein H2 expression and the translocation of CUG-binding protein 1 from the nucleus to the cytoplasm. The UV-induced increase in SHMT1 translation is accompanied by an increase in the small ubiquitin-like modifier-dependent nuclear localization of the de novo thymidylate biosynthesis pathway and a decrease in DNA strand breaks, indicating a role for SHMT1 and nuclear folate metabolism in DNA repair.
Fox
Jennifer T
JT
Graduate Field of Biochemistry and Molecular and Cellular Biology, Cornell University, Ithaca, New York 14853, USA.
Shin
William K
WK
Caudill
Marie A
MA
Stover
Patrick J
PJ
D020121:5' Untranslated Regions; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D015870:Gene Expression / Q000528:radiation effects*; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics* / Q000378:metabolism; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010442:Peptide Chain Initiation, Translational / Q000528:radiation effects*; D011485:Protein Binding; D021381:Protein Transport / Q000528:radiation effects; D014466:Ultraviolet Rays
D020121:5' Untranslated Regions; C116747:HNRNPH2 protein, human; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human