Defective telomere lagging strand synthesis in cells lacking WRN helicase activity

Laure Crabbe, Ramiro E Verdun, Candy I. Haggblom, Jan Karlseder

Research output: Contribution to journalArticle

441 Citations (Scopus)

Abstract

Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.

Original languageEnglish
Pages (from-to)1951-1953
Number of pages3
JournalScience
Volume306
Issue number5703
DOIs
StatePublished - Dec 10 2004
Externally publishedYes

Fingerprint

Telomere
Genomic Instability
RecQ Helicases
Werner Syndrome
Telomere Shortening
Chromatids
Telomerase
Siblings
DNA
Growth

ASJC Scopus subject areas

  • General

Cite this

Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. / Crabbe, Laure; Verdun, Ramiro E; Haggblom, Candy I.; Karlseder, Jan.

In: Science, Vol. 306, No. 5703, 10.12.2004, p. 1951-1953.

Research output: Contribution to journalArticle

Crabbe, Laure ; Verdun, Ramiro E ; Haggblom, Candy I. ; Karlseder, Jan. / Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. In: Science. 2004 ; Vol. 306, No. 5703. pp. 1951-1953.
@article{95d3f72152d34cbabfff830bca58d9e0,
title = "Defective telomere lagging strand synthesis in cells lacking WRN helicase activity",
abstract = "Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.",
author = "Laure Crabbe and Verdun, {Ramiro E} and Haggblom, {Candy I.} and Jan Karlseder",
year = "2004",
month = "12",
day = "10",
doi = "10.1126/science.1103619",
language = "English",
volume = "306",
pages = "1951--1953",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5703",

}

TY - JOUR

T1 - Defective telomere lagging strand synthesis in cells lacking WRN helicase activity

AU - Crabbe, Laure

AU - Verdun, Ramiro E

AU - Haggblom, Candy I.

AU - Karlseder, Jan

PY - 2004/12/10

Y1 - 2004/12/10

N2 - Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.

AB - Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.

UR - http://www.scopus.com/inward/record.url?scp=10344256183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10344256183&partnerID=8YFLogxK

U2 - 10.1126/science.1103619

DO - 10.1126/science.1103619

M3 - Article

C2 - 15591207

AN - SCOPUS:10344256183

VL - 306

SP - 1951

EP - 1953

JO - Science

JF - Science

SN - 0036-8075

IS - 5703

ER -