The broken genome

Genetic and pharmacologic approaches to breaking DNA

Leslie L. Woo, Kenan Onel, Nathan Ellis

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The RecQ family of DNA helicases consists of specialized DNA unwinding enzymes that promote genomic stability through their participation in a number of cellular processes, including DNA replication, recombination, DNA damage signaling, and DNA repair pathways. Mutations resulting in the inactivation of some but not all members of the RecQ helicase family can lead to human syndromes which are characterized by marked chromosomal instability and an increased predisposition to cancer. An evolutionarily conserved interaction between RecQ helicases and topoisomerase 3s has been established, and this interaction is important in the regulation of recombination and genomic stability. Topoisomerases are critical in the cell because they relieve helical stress that arises when DNA is unwound. Topoisomerases function by breaking and rejoining DNA. By inhibition of the rejoining function, topoisomerase inhibitors are potent chemotherapeutic agents that have been used successfully in the treatment of hematologic malignancies and other cancers. This review discusses the roles of RecQ helicases in genomic stability, the interplay between RecQ helicases and topoisomerase 3s, and current and future prospects for targeting these interactions to develop novel anticancer therapies.

Original languageEnglish (US)
Pages (from-to)208-218
Number of pages11
JournalAnnals of Medicine
Volume39
Issue number3
DOIs
StatePublished - 2007
Externally publishedYes

Fingerprint

RecQ Helicases
Genome
Genomic Instability
DNA
Genetic Recombination
Topoisomerase Inhibitors
Chromosomal Instability
Hematologic Neoplasms
DNA Replication
DNA Repair
DNA Damage
Neoplasms
Mutation
Enzymes
Therapeutics

Keywords

  • Anticancer therapies
  • Bloom syndrome (BS)
  • Cancer
  • DNA repair
  • Genomic instability
  • Recombination
  • RecQ helicases
  • Topoisomerase 3s
  • Topoisomerase inhibitors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The broken genome : Genetic and pharmacologic approaches to breaking DNA. / Woo, Leslie L.; Onel, Kenan; Ellis, Nathan.

In: Annals of Medicine, Vol. 39, No. 3, 2007, p. 208-218.

Research output: Contribution to journalArticle

Woo, Leslie L. ; Onel, Kenan ; Ellis, Nathan. / The broken genome : Genetic and pharmacologic approaches to breaking DNA. In: Annals of Medicine. 2007 ; Vol. 39, No. 3. pp. 208-218.
@article{48b053c23885449395e00c3013550d1b,
title = "The broken genome: Genetic and pharmacologic approaches to breaking DNA",
abstract = "The RecQ family of DNA helicases consists of specialized DNA unwinding enzymes that promote genomic stability through their participation in a number of cellular processes, including DNA replication, recombination, DNA damage signaling, and DNA repair pathways. Mutations resulting in the inactivation of some but not all members of the RecQ helicase family can lead to human syndromes which are characterized by marked chromosomal instability and an increased predisposition to cancer. An evolutionarily conserved interaction between RecQ helicases and topoisomerase 3s has been established, and this interaction is important in the regulation of recombination and genomic stability. Topoisomerases are critical in the cell because they relieve helical stress that arises when DNA is unwound. Topoisomerases function by breaking and rejoining DNA. By inhibition of the rejoining function, topoisomerase inhibitors are potent chemotherapeutic agents that have been used successfully in the treatment of hematologic malignancies and other cancers. This review discusses the roles of RecQ helicases in genomic stability, the interplay between RecQ helicases and topoisomerase 3s, and current and future prospects for targeting these interactions to develop novel anticancer therapies.",
keywords = "Anticancer therapies, Bloom syndrome (BS), Cancer, DNA repair, Genomic instability, Recombination, RecQ helicases, Topoisomerase 3s, Topoisomerase inhibitors",
author = "Woo, {Leslie L.} and Kenan Onel and Nathan Ellis",
year = "2007",
doi = "10.1080/08035250601167136",
language = "English (US)",
volume = "39",
pages = "208--218",
journal = "Annals of Medicine",
issn = "0785-3890",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - The broken genome

T2 - Genetic and pharmacologic approaches to breaking DNA

AU - Woo, Leslie L.

AU - Onel, Kenan

AU - Ellis, Nathan

PY - 2007

Y1 - 2007

N2 - The RecQ family of DNA helicases consists of specialized DNA unwinding enzymes that promote genomic stability through their participation in a number of cellular processes, including DNA replication, recombination, DNA damage signaling, and DNA repair pathways. Mutations resulting in the inactivation of some but not all members of the RecQ helicase family can lead to human syndromes which are characterized by marked chromosomal instability and an increased predisposition to cancer. An evolutionarily conserved interaction between RecQ helicases and topoisomerase 3s has been established, and this interaction is important in the regulation of recombination and genomic stability. Topoisomerases are critical in the cell because they relieve helical stress that arises when DNA is unwound. Topoisomerases function by breaking and rejoining DNA. By inhibition of the rejoining function, topoisomerase inhibitors are potent chemotherapeutic agents that have been used successfully in the treatment of hematologic malignancies and other cancers. This review discusses the roles of RecQ helicases in genomic stability, the interplay between RecQ helicases and topoisomerase 3s, and current and future prospects for targeting these interactions to develop novel anticancer therapies.

AB - The RecQ family of DNA helicases consists of specialized DNA unwinding enzymes that promote genomic stability through their participation in a number of cellular processes, including DNA replication, recombination, DNA damage signaling, and DNA repair pathways. Mutations resulting in the inactivation of some but not all members of the RecQ helicase family can lead to human syndromes which are characterized by marked chromosomal instability and an increased predisposition to cancer. An evolutionarily conserved interaction between RecQ helicases and topoisomerase 3s has been established, and this interaction is important in the regulation of recombination and genomic stability. Topoisomerases are critical in the cell because they relieve helical stress that arises when DNA is unwound. Topoisomerases function by breaking and rejoining DNA. By inhibition of the rejoining function, topoisomerase inhibitors are potent chemotherapeutic agents that have been used successfully in the treatment of hematologic malignancies and other cancers. This review discusses the roles of RecQ helicases in genomic stability, the interplay between RecQ helicases and topoisomerase 3s, and current and future prospects for targeting these interactions to develop novel anticancer therapies.

KW - Anticancer therapies

KW - Bloom syndrome (BS)

KW - Cancer

KW - DNA repair

KW - Genomic instability

KW - Recombination

KW - RecQ helicases

KW - Topoisomerase 3s

KW - Topoisomerase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=34247580152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247580152&partnerID=8YFLogxK

U2 - 10.1080/08035250601167136

DO - 10.1080/08035250601167136

M3 - Article

VL - 39

SP - 208

EP - 218

JO - Annals of Medicine

JF - Annals of Medicine

SN - 0785-3890

IS - 3

ER -