DNA replication stress and its impact on chromosome segregation and tumorigenesis

TY - JOUR

T1 - DNA replication stress and its impact on chromosome segregation and tumorigenesis

AU - Zhang, Bi Ning

AU - Bueno Venegas, Andrés

AU - Hickson, Ian D.

AU - Chu, Wai Kit

PY - 2019/4

Y1 - 2019/4

N2 - Genome instability and cell cycle dysregulation are commonly associated with cancer. DNA replication stress driven by oncogene activation during tumorigenesis is now well established as a source of genome instability. Replication stress generates DNA damage not only during S phase, but also in the subsequent mitosis, where it impacts adversely on chromosome segregation. Some regions of the genome seem particularly sensitive to replication stress-induced instability; most notably, chromosome fragile sites. In this article, we review some of the important issues that have emerged in recent years concerning DNA replication stress and fragile site expression, as well as how chromosome instability is minimized by a family of ring-shaped protein complexes known as SMC proteins. Understanding how replication stress impacts on S phase and mitosis in cancer should provide opportunities for the development of novel and tumour-specific treatments.

AB - Genome instability and cell cycle dysregulation are commonly associated with cancer. DNA replication stress driven by oncogene activation during tumorigenesis is now well established as a source of genome instability. Replication stress generates DNA damage not only during S phase, but also in the subsequent mitosis, where it impacts adversely on chromosome segregation. Some regions of the genome seem particularly sensitive to replication stress-induced instability; most notably, chromosome fragile sites. In this article, we review some of the important issues that have emerged in recent years concerning DNA replication stress and fragile site expression, as well as how chromosome instability is minimized by a family of ring-shaped protein complexes known as SMC proteins. Understanding how replication stress impacts on S phase and mitosis in cancer should provide opportunities for the development of novel and tumour-specific treatments.

KW - Common fragile sites

KW - DNA replication stress

KW - MiDAS

KW - SMC proteins

U2 - 10.1016/j.semcancer.2018.04.005

DO - 10.1016/j.semcancer.2018.04.005

M3 - Journal article

C2 - 29692334

AN - SCOPUS:85046161578

SN - 1044-579X

VL - 55

SP - 61

EP - 69

JO - Seminars in Cancer Biology

JF - Seminars in Cancer Biology

ER -