Duplex DNA from sites of helicase-polymerase uncoupling links non-B DNA structure formation to replicative stress

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Amparo, Camille, Clark, Jarrod, Bedell, Victoria, Murata-Collins, Joyce L., Martella, Marianna, Pichiorri, Flavia, Warner, Emily F., Abdelhamid, Mahmoud A. S., Waller, Zoë A. E. and Smith, Steven S. (2020) Duplex DNA from sites of helicase-polymerase uncoupling links non-B DNA structure formation to replicative stress. Cancer Genomics & Proteomics, 17 (2). pp. 101-115. ISSN 1109-6535

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: cmg helicase uncoupling,g-quadruplex,i-motif,replication stress,biochemistry,molecular biology,genetics,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups: Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
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Depositing User: LivePure Connector
Date Deposited: 03 Apr 2020 00:46
Last Modified: 25 Sep 2024 14:35
URI: https://ueaeprints.uea.ac.uk/id/eprint/74700
DOI: 10.21873/cgp.20171

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