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ATM signaling delays skin pigmentation upon UV exposure by mediating MITF function towards DNA repair mode

ABSTRACT: Skin pigmentation is paused following sun exposure, however the mechanism behind this pausing is unknown. Here we found that the UVB-induced DNA repair system, led by the ATM protein kinase, represses MITF transcriptional activity of pigmentation genes while placing MITF in DNA repair mode, thus directly inhibiting pigment production. Phosphoproteomics analysis revealed ATM to be the most significantly enriched pathway among all UVB-induced DNA repair systems. ATM inhibition in mouse or human skin, either genetically or chemically, induces pigmentation. Upon UVB, MITF transcriptional activation is blocked due to ATM dependent phosphorylation of MITF on S414, which modifies MITF activity and interactome towards DNA repair including binding to TRIM28 and RBBP4. Accordingly, MITF genome-occupancy is enriched in sites of high DNA damage that are likely repaired. This suggests that ATM harnesses the pigmentation key activator, for the necessary rapid, efficient DNA repair, thus optimizing the chances of the cell to survive.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte

SUBMITTER: Tamar Ziv

LAB HEAD: Carmit Levy

PROVIDER: PXD041121 | Pride | 2023-07-19

REPOSITORIES: Pride

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			Action	DRS
	68015txt.rar	Other
	69293_70247txt.rar	Other
	Seq68015_phos_HF.raw	Raw
	Seq68018_phos_HF.raw	Raw
	Seq69293_phos_HF.raw	Raw

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