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

Camille Amparo; Jarrod Clark; Victoria Bedell; Joyce L. Murata-Collins; Marianna Martella; Flavia Pichiorri; Emily F. Warner; Mahmoud A. S. Abdelhamid; Zoë A. E. Waller; Steven S. Smith

doi:10.21873/cgp.20171

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

Camille Amparo, Jarrod Clark, Victoria Bedell, Joyce L. Murata-Collins, Marianna Martella, Flavia Pichiorri, Emily F. Warner, Mahmoud A. S. Abdelhamid, Zoë A. E. Waller, Steven S. Smith

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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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.

Original language	English
Pages (from-to)	101-115
Number of pages	15
Journal	Cancer Genomics & Proteomics
Volume	17
Issue number	2
DOIs	https://doi.org/10.21873/cgp.20171
Publication status	Published - Mar 2020

Keywords

CMG helicase uncoupling
G-quadruplex
i-motif
replication stress

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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. ; Smith, Steven S. / Duplex DNA from sites of helicase-polymerase uncoupling links non-B DNA structure formation to replicative stress. In: Cancer Genomics & Proteomics. 2020 ; Vol. 17, No. 2. pp. 101-115.

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

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.",

keywords = "CMG helicase uncoupling, G-quadruplex, i-motif, replication stress",

author = "Camille Amparo and Jarrod Clark and Victoria Bedell and Murata-Collins, {Joyce L.} and Marianna Martella and Flavia Pichiorri and Warner, {Emily F.} and Abdelhamid, {Mahmoud A. S.} and Waller, {Zo{\"e} A. E.} and Smith, {Steven S.}",

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Duplex DNA from sites of helicase-polymerase uncoupling links non-B DNA structure formation to replicative stress. / 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.; Smith, Steven S.

In: Cancer Genomics & Proteomics, Vol. 17, No. 2, 03.2020, p. 101-115.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Duplex DNA from sites of helicase-polymerase uncoupling links non-B DNA structure formation to replicative stress

AU - Amparo, Camille

AU - Clark, Jarrod

AU - Bedell, Victoria

AU - Murata-Collins, Joyce L.

AU - Martella, Marianna

AU - Pichiorri, Flavia

AU - Warner, Emily F.

AU - Abdelhamid, Mahmoud A. S.

AU - Waller, Zoë A. E.

AU - Smith, Steven S.

PY - 2020/3

Y1 - 2020/3

N2 - 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.

AB - 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.

KW - CMG helicase uncoupling

KW - G-quadruplex

KW - i-motif

KW - replication stress

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DO - 10.21873/cgp.20171

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JO - Cancer Genomics & Proteomics

JF - Cancer Genomics & Proteomics

SN - 1109-6535

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ER -

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

Abstract

Keywords

UN SDGs

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