The ATR barrier to replication-born DNA damage

TY - JOUR

T1 - The ATR barrier to replication-born DNA damage

AU - López-Contreras, Andrés J

AU - Fernandez-Capetillo, Oscar

N1 - Copyright © 2010 Elsevier B.V. All rights reserved.

PY - 2010/12/10

Y1 - 2010/12/10

N2 - Replication comes with a price. The molecular gymnastics that occur on DNA during its duplication frequently derive to a wide spectrum of abnormalities which are still far from understood. These are brought together under the unifying term "replicative stress" (RS) which likely stands for large and unprotected regions of single-stranded DNA (ssDNA). In addition to RS, recombinogenic stretches of ssDNA are also formed at resected DNA double strand breaks (DSBs). Both situations converge on a ssDNA intermediate, which is the triggering signal for a damage situation. The cellular response in both cases is coordinated by a phosphorylation-based signaling cascade that starts with the activation of the ATR (ATM and Rad3-related) kinase. Given that ATR is essential for replicating cells, understanding the consequences of a defective ATR response for a mammalian organism has been limited until recent years. We here discuss on the topic and review the findings that connect ATR to ageing and cancer.

AB - Replication comes with a price. The molecular gymnastics that occur on DNA during its duplication frequently derive to a wide spectrum of abnormalities which are still far from understood. These are brought together under the unifying term "replicative stress" (RS) which likely stands for large and unprotected regions of single-stranded DNA (ssDNA). In addition to RS, recombinogenic stretches of ssDNA are also formed at resected DNA double strand breaks (DSBs). Both situations converge on a ssDNA intermediate, which is the triggering signal for a damage situation. The cellular response in both cases is coordinated by a phosphorylation-based signaling cascade that starts with the activation of the ATR (ATM and Rad3-related) kinase. Given that ATR is essential for replicating cells, understanding the consequences of a defective ATR response for a mammalian organism has been limited until recent years. We here discuss on the topic and review the findings that connect ATR to ageing and cancer.

KW - Aging

KW - Ataxia Telangiectasia Mutated Proteins

KW - Cell Cycle Proteins

KW - DNA Breaks, Double-Stranded

KW - DNA Repair

KW - DNA Replication

KW - DNA, Single-Stranded

KW - Models, Biological

KW - Neoplasms

KW - Phosphorylation

KW - Protein Kinases

KW - Protein-Serine-Threonine Kinases

KW - Signal Transduction

U2 - 10.1016/j.dnarep.2010.09.012

DO - 10.1016/j.dnarep.2010.09.012

M3 - Journal article

C2 - 21036674

SN - 1568-7864

VL - 9

SP - 1249

EP - 1255

JO - DNA Repair

JF - DNA Repair

IS - 12

ER -