Camille Amparo1,2, Jarrod Clark1,2, Victoria Bedell3, Joyce L Murata-Collins3, Marianna Martella4,5, Flavia Pichiorri4,5, Emily F Warner6, Mahmoud A S Abdelhamid6, Zoë A E Waller6, Steven S Smith7,5. 1. Division of Urology, City of Hope National Medical Center, Duarte, CA, U.S.A. 2. Beckman Research Institute, City of Hope, Duarte, CA, U.S.A. 3. Division of Cytogenetics, City of Hope National Medical Center, Duarte, CA, U.S.A. 4. Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope National Medical Center, Duarte, CA, U.S.A. 5. Hematological Malignancies and Translational Science, City of Hope National Medical Center, Duarte, CA, U.S.A. 6. School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, U.K. 7. Beckman Research Institute, City of Hope, Duarte, CA, U.S.A. ssmith@coh.org.
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. Copyright
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. Copyright
Authors: Wouter Koole; Robin van Schendel; Andrea E Karambelas; Jane T van Heteren; Kristy L Okihara; Marcel Tijsterman Journal: Nat Commun Date: 2014 Impact factor: 14.919
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Authors: Marianna Martella; Flavia Pichiorri; Rupesh V Chikhale; Mahmoud A S Abdelhamid; Zoë A E Waller; Steven S Smith Journal: Nucleic Acids Res Date: 2022-04-08 Impact factor: 16.971