A role for dormant origins in tumor suppression

Abstract

In this issue of Molecular Cell, Kawabata et al. (2011) show that mice hypomorphic for the replication licensing protein Mcm4 show spontaneous DNA replication defects due to a lack of dormant origins, potentially explaining why these mice are cancer-prone.

Figure 1

A role for dormant origins in maintaining genomic stability. A small segment of the genome is shown during the cell cycle of normal (top) and MCM hypomorphic (bottom) cells. In G1, efficient and normally dormant (inefficient) origins are licensed by loading MCM2-7 onto chromatin (green and light green dots). In S-phase, some origins fire (red dots) and replication forks move bidirectionally away from them, passively replicating other origins (grey dots) until forks stall or terminate. Fork stalling triggers the firing of some origins that usually remain dormant (light red dots) to ensure complete genome duplication. Lack of dormant origins can result in progression of cells into mitosis with unreplicated segments of the genome, leading to chromosome breakage and formation of micronuclei.