Differences

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--- dna [2026/01/30 22:31] – [Epigenetics] gary1
+++ dna [2026/01/30 22:58] (current) – [DNA damage and repair] gary1
@@ Line 145: / Line 145: @@
   ***DNA-protein cross-links (DPCs)**
     * these are highly toxic lesions in which proteins become covalently attached to DNA, blocking essential processes such as replication and transcription and thus these need to be removed to ensure the cell's genomic stability and ability to divide
+    * DPCs can result from:
+      * natural cellular activities:
+        * Reactive Oxygen Species (ROS)
+        * reactive aldehydes:
+          * endogenous aldehydes (e.g., formaldehyde, malondialdehyde) act as bridges, cross-linking protein amino groups to DNA bases
+        * topoisomerase trapping:
+          * during DNA replication or transcription, TOP1 or TOP2 enzymes can become covalently trapped on DNA when trying to relieve tension, forming Top-DPCs
+      * exogenous issues:
+        * UV radiation
+        *excessive alcohol drinking increasing aldehydes
+        *cytotoxic drugs
+        *toxins
+          * exposure to chromium (Cr), nickel (Ni), and formaldehyde
     * the protease SPRTN was the first enzyme identified to resolve these lesions by cleaving the protein component from DNA - SPRTN repairs DPCs not only during replication (S phase) but also mitosis (M phase)
+    * inherited inactivating mutations in SPRTN cause Ruijs-Aalfs progeria syndrome (RJALS), a rare disorder marked by premature aging and early-onset liver cancer
     * if this repair process is inadequate, DPCs can leak into the cytoplasm which activates the cGAS-STING [[innate_immunity|innate immune]] pathway through recognition of cytosolic DNA and micronuclei and this activation can result in cell death (([[https://www.science.org/doi/10.1126/science.adx9445|2026: DNA-protein cross-links promote cGAS-STING–driven premature aging and embryonic lethality]]))