DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities

TY - JOUR

T1 - DNA replication and cancer

T2 - From dysfunctional replication origin activities to therapeutic opportunities

AU - Boyer, Anne-Sophie

AU - Walter, David

AU - Sørensen, Claus Storgaard

N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy.

AB - A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy.

KW - Journal Article

KW - Review

U2 - 10.1016/j.semcancer.2016.01.001

DO - 10.1016/j.semcancer.2016.01.001

M3 - Review

C2 - 26805514

SN - 1044-579X

VL - 37-38

SP - 16

EP - 25

JO - Seminars in Cancer Biology

JF - Seminars in Cancer Biology

ER -