The "enemies within": regions of the genome that are inherently difficult to replicate

TY - JOUR

T1 - The "enemies within"

T2 - regions of the genome that are inherently difficult to replicate

AU - Bhowmick, Rahul

AU - Hickson, Ian D

PY - 2017

Y1 - 2017

N2 - An unusual feature of many eukaryotic genomes is the presence of regions that appear intrinsically difficult to copy during the process of DNA replication. Curiously, the location of these difficult-to-replicate regions is often conserved between species, implying a valuable role in some aspect of genome organization or maintenance. The most prominent class of these regions in mammalian cells is defined as chromosome fragile sites, which acquired their name because of a propensity to form visible gaps/breaks on otherwise-condensed chromosomes in mitosis. This fragility is particularly apparent following perturbation of DNA replication-a phenomenon often referred to as "replication stress". Here, we review recent data on the molecular basis for chromosome fragility and the role of fragile sites in the etiology of cancer. In particular, we highlight how studies on fragile sites have provided unexpected insights into how the DNA repair machinery assists in the completion of DNA replication.

AB - An unusual feature of many eukaryotic genomes is the presence of regions that appear intrinsically difficult to copy during the process of DNA replication. Curiously, the location of these difficult-to-replicate regions is often conserved between species, implying a valuable role in some aspect of genome organization or maintenance. The most prominent class of these regions in mammalian cells is defined as chromosome fragile sites, which acquired their name because of a propensity to form visible gaps/breaks on otherwise-condensed chromosomes in mitosis. This fragility is particularly apparent following perturbation of DNA replication-a phenomenon often referred to as "replication stress". Here, we review recent data on the molecular basis for chromosome fragility and the role of fragile sites in the etiology of cancer. In particular, we highlight how studies on fragile sites have provided unexpected insights into how the DNA repair machinery assists in the completion of DNA replication.

U2 - 10.12688/f1000research.11024.1

DO - 10.12688/f1000research.11024.1

M3 - Review

C2 - 28620461

SN - 2046-1402

VL - 6

JO - F1000Research

JF - F1000Research

M1 - 666

ER -