DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing

Abstract

SUMMARY Ultraviolet (UV) radiation is a carcinogen that generates DNA lesions. Here we demonstrate an unexpected role for DGCR8, an RNA binding protein that canonically functions with Drosha to mediate microRNA processing, in the repair of UV-induced DNA lesions. Treatment with UV induced phosphorylation on Serine 153 (S153) of DGCR8 in human and murine cells. S153 phosphorylation was critical for cellular resistance to UV, the removal of UV-induced DNA lesions, and the recovery of RNA synthesis after UV exposure, but not for microRNA expression. The RNA-binding and Drosha-binding activities of DGCR8 were not critical for UV resistance. DGCR8 depletion was epistatic to defects in XPA, CSA and CSB for UV sensitivity. DGCR8 physically interacted with CSB and RNA polymerase II. JNKs were involved in the UV-induced S153 phosphorylation. These findings suggest that UV-induced S153 phosphorylation mediates transcription-coupled nucleotide excision repair of UV-induced DNA lesions in a manner independent of microRNA processing.

Noncanonical functions of microRNA pathway enzymes – Drosha, DGCR8, Dicer and Ago proteins

“…The Microprocessor complex can destabilise DGCR8 mRNA and create a feedback loop that regulates its own levels . Normally, Drosha and DGCR8 act as a complex to generate pre‐miRNAs in the nucleus but sometimes the proteins can also act independently to carry out their noncanonical functions, for instance, in the case of participation of DGCR8 in transcription‐coupled NER . Future studies should look carefully at the individual roles of Drosha and DGCR8 to better comprehend the relationship between these two enzymes in the context of their noncanonical functions.…”

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

“…Proteins encoded by Bmi1, Dgcr8, Dicer1, Elp1, Ercc1, Ercc6, Msi1, Sirt6, Top2b, Ubb, and Uchl3 are known to participate in the DNA damage response [387,[389][390][391][392][393][394][395][396][397][398], some in transcription-coupled DNA repair. For example, BMI1 represses transcription at sites of UV-induced DNA damage to allow repair [389]; ELP1 is a required component of the Elongator complex [399], which couples RNA polymerase II to an alkyladenine glycosylase that initiates base excision repair [392]; ERCC6 promotes DSB repair in actively transcribed regions by displacing RNA polymerase from the lesion site [387], and DGCR8 interacts with both RNA polymerase II and ERCC6 to mediate transcription-coupled nucleotide excision repair of UV-induced DNA lesions [390]. Intriguingly, topoisomerase TOP2B, which creates DSBs during transcriptional activation [396], has been identified as a key regulator of transcription during the last stages of postnatal PR development [400].…”

The effect of ultraviolet modification of Acetobacter xylinum (CGMCC No. 7431) and the use of coconut milk on the yield and quality of bacterial cellulose

“…The growth of a single colony of A. xylinum from UV mutagenesis for 5 min was very low. The reason for the low growth rate may be because at long exposure the base groups of A. xylinum could not be matched properly (Calses et al, 2017), and therefore, their growth was inhibited. Figure 2 c1 shows the BC found in a medium containing coconut milk using a strain from UV mutagenesis for 4 min.…”