Abstract

Maintenance of genomic stability is critical for living organisms because it is crucial for cell survival and development, and it prevents the development of deleterious mutations. Overriding this control will cause genomic instability, a hallmark of cancer. The genome is highly vulnerable to damage, especially during DNA replication because chromosome is decondensed and the replication forks are extremely sensitive to DNA damage agents. The eukaryotic replisome, which consists of a large number of replication fork-associated proteins, is essential for the elongation of replication forks during DNA replication. This complex contains DNA polymerases, MCM helicase, single stranded DNA (ssDNA) binding protein RPA, sliding clamp PCNA, Tipin, Timeless, Claspin, And-1, etc. In cells with DNA damage such as replication stress, replication forks are stalled Figure 1. At stalled replication forks, some of replisome components switch their role from facilitating DNA synthesis to inducing activation of DNA replication checkpoint, a signaling transduction pathway that is critical to maintain fork stability and triggers cell cycle arrest.

Highlights

  • Maintenance of genomic stability is critical for living organisms because it is crucial for cell survival and development, and it prevents the development of deleterious mutations

  • The genome is highly vulnerable to damage, especially during DNA replication because chromosome is decondensed and the replication forks are extremely sensitive to DNA damage agents

  • At stalled replication forks, some of replisome components switch their role from facilitating DNA synthesis to inducing activation of DNA replication checkpoint, a signaling transduction pathway that is critical to maintain fork stability and triggers cell cycle arrest

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Summary

Introduction

Maintenance of genomic stability is critical for living organisms because it is crucial for cell survival and development, and it prevents the development of deleterious mutations. Maintain Genomic Stability: Multitask of DNA Replication Proteins Jing Hao and Wenge Zhu* Department of Biochemistry and Molecular Medicine, The George Washington University Medical School, 2300 Eye Street N.W., Washington, DC 20037, USA This complex contains DNA polymerases, MCM helicase, single stranded DNA (ssDNA) binding protein RPA, sliding clamp PCNA, Tipin, Timeless, Claspin, And-1, etc.

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