Replication Fork Reversal and Protection

Shan Qiu; Guixing Jiang; Liping Cao; Jun Huang

doi:10.3389/fcell.2021.670392

Replication Fork Reversal and Protection

Front Cell Dev Biol. 2021 May 10:9:670392. doi: 10.3389/fcell.2021.670392. eCollection 2021.

Authors

Shan Qiu^{1

2

3}, Guixing Jiang¹, Liping Cao¹, Jun Huang^{1

2}

Affiliations

¹ Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² The MOE Key Laboratory of Biosystems Homeostasis and Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China.
³ Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, China.

Abstract

During genome replication, replication forks often encounter obstacles that impede their progression. Arrested forks are unstable structures that can give rise to collapse and rearrange if they are not properly processed and restarted. Replication fork reversal is a critical protective mechanism in higher eukaryotic cells in response to replication stress, in which forks reverse their direction to form a Holliday junction-like structure. The reversed replication forks are protected from nuclease degradation by DNA damage repair proteins, such as BRCA1, BRCA2, and RAD51. Some of these molecules work cooperatively, while others have unique functions. Once the stress is resolved, the replication forks can restart with the help of enzymes, including human RECQ1 helicase, but restart will not be considered here. Here, we review research on the key factors and mechanisms required for the remodeling and protection of stalled replication forks in mammalian cells.

Keywords: DNA translocase; genome instability; replication fork reversal; replication fork stalling; replication stress.

Publication types

Review