Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retroposed copies (RPCs) of genes are functional (intronless paralogs) or nonfunctional (processed pseudogenes) copies derived from mRNA through a process of retrotransposition. Previous studies found that gene families involved in mRNA translation or nuclear function were more likely to have large numbers of RPCs. Here we characterize RPCs of the few families coding for the abundant high-mobility-group (HMG) proteins in humans. Using an algorithm we developed, we identified and studied 219 HMG RPCs. For slightly more than 10% of these RPCs, we found evidence indicating expression. Furthermore, eight of these are potentially new members of the HMG families of proteins. For three RPCs, the evidence indicated expression as part of other transcripts; in all of these, we found the presence of alternative splicing or multiple polyadenylation signals. RPC distribution among the HMGs was not even, with 33-65 each for HMGB1, HMGB3, HMGN1, and HMGN2, and 0-6 each for HMGA1, HMGA2, HMGB2, and HMGN3. Analysis of the sequences flanking the RPCs revealed that the junction between the target site duplications and the 5'-flanking sequences exhibited the same TT/AAAA consensus found for the L1 endonuclease, supporting an L1-mediated retrotransposition mechanism. Finally, because our algorithm included aligning RPC flanking sequences with the corresponding HMG genomic sequence, we were able to identify transcribed regions of HMG genes that were not part of the published mRNA sequences.
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PMID:Retroposed copies of the HMG genes: a window to genome dynamics. 1272

A network of DNA damage surveillance systems is triggered by sensing of DNA lesions and the initiation of a signal transduction cascade that activates genome-protection pathways including nucleotide excision repair (NER). NER operates through coordinated assembly of repair factors into pre- and post-incision complexes. Recent work identifies RPA as a key regulator of the transition from dual incision to repair-synthesis in UV-irradiated non-cycling cells, thereby averting the generation of unprocessed repair intermediates. These intermediates could lead to recombinogenic events and trigger a persistent ATR-dependent checkpoint signaling. It is now evident that DNA damage signaling is not limited to NER proficient cells. ATR-dependent checkpoint activation also occurs in UV-exposed non-cycling repair deficient cells coinciding with the formation of endonuclease APE1-mediated DNA strand breaks. In addition, the encounter of elongating RNA polymerase II (RNAPIIo) with DNA damage lesions and its persistent stalling provides a strong DNA damage signaling leading to cell cycle arrest, apoptosis and increased mutagenesis. The mechanism underlying the strong and strand specific induction of UV-induced mutations in NER deficient cells has been recently resolved by the finding that gene transcription itself increases UV-induced mutagenesis in a strand specific manner via increased deamination of cytosines. The cell removes the RNAPIIo-blocking DNA lesions by transcription-coupled repair (TC-NER) without displacement of the DNA damage stalled RNAPIIo. Deficiency in TC-NER associates with mutations in the CSA and CSB genes giving rise to the rare human disorder Cockayne syndrome (CS). CSB functions as a repair coupling factor to attract NER proteins, chromatin remodelers and the CSA-E3-ubiquitin ligase complex to the stalled RNAPIIo; CSA is dispensable for attraction of NER proteins, yet in cooperation with CSB is required to recruit XAB2, the nucleosomal binding protein HMGN1 and TFIIS. The molecular mechanisms by which these proteins bring about efficient TC-NER and trigger signaling after transcription arrest remain elusive; particularly the role of chromatin remodeling in TC-NER needs to be clarified in the context of anticipated structural changes that allow repair and transcription restart.
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PMID:DNA damage response and transcription. 2162 31