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

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

12 Citations (Scopus)

45 Downloads (Pure)

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

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

CMG helicase uncoupling
G-quadruplex
i-motif
replication stress

Access to Document

10.21873/cgp.20171

Published_VersionFinal published version, 945 KB

Cite this

@article{d4a5e9d68a964667930b6d150bb26540,

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.\}",

year = "2020",

month = mar,

doi = "10.21873/cgp.20171",

language = "English",

volume = "17",

pages = "101--115",

journal = "Cancer Genomics \& Proteomics",

issn = "1109-6535",

publisher = "International Institute of Anticancer Research",

number = "2",

}

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

UR - https://www.scopus.com/pages/publications/85082092574

U2 - 10.21873/cgp.20171

DO - 10.21873/cgp.20171

M3 - Article

C2 - 32108033

SN - 1109-6535

VL - 17

SP - 101

EP - 115

JO - Cancer Genomics & Proteomics

JF - Cancer Genomics & Proteomics

IS - 2

ER -

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

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Cite this