Duplex DNA from Sites of Helicase-Polymerase Uncoupling Links Non-B DNA Structure Formation to Replicative Stress
| Autor: | Camille Amparo, Joyce Murata-Collins, Zoë A. E. Waller, Flavia Pichiorri, Mahmoud A. S. Abdelhamid, Jarrod Clark, Steven S. Smith, Victoria Bedell, Emily F. Warner, Marianna Martella |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cloning
DNA Replication Cancer Research Dna duplex biology Chemistry DNA Helicases Helicase Sequence Analysis DNA G-quadruplex Biochemistry Cell biology 03 medical and health sciences 0302 clinical medicine Cell culture 030220 oncology & carcinogenesis Genetics biology.protein Humans Gene sequence Molecular Biology Polymerase Sequence (medicine) Research Article DNA Polymerase III |
| Popis: | Background Replication impediments can produce helicase-polymerase uncoupling allowing lagging strand synthesis to continue for as much as 6 kb from the site of the impediment. Materials and methods We developed a cloning procedure designed to recover fragments from lagging strand near the helicase halt site. Results A total of 62% of clones from a p53-deficient tumor cell line (PC3) and 33% of the clones from a primary cell line (HPS-19I) were within 5 kb of a G-quadruplex forming sequence. Analyses of a RACK7 gene sequence, that was cloned multiple times from the PC3 line, revealed multiple deletions in region about 1 kb from the cloned region that was present in a non-B conformation. Sequences from the region formed G-quadruplex and i-motif structures under physiological conditions. Conclusion Defects in components of non-B structure suppression systems (e.g. p53 helicase targeting) promote replication-linked damage selectively targeted to sequences prone to G-quadruplex and i-motif formation. |
| Databáze: | OpenAIRE |
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