The Intra-S Checkpoint Responses to DNA Damage

Genes

Nicholas Rhind¹  Divya Ramalingam Iyer² 

[1] Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA;;Department of Biochemistry &

关键词: DNA damage;    intra-S checkpoint;    ATR;    Chk1;    fork stability;    origin regulation;   

DOI  :  10.3390/genes8020074

来源: DOAJ

【 摘 要 】

Faithful duplication of the genome is a challenge because DNA is susceptible to damage by a number of intrinsic and extrinsic genotoxins, such as free radicals and UV light. Cells activate the intra-S checkpoint in response to damage during S phase to protect genomic integrity and ensure replication fidelity. The checkpoint prevents genomic instability mainly by regulating origin firing, fork progression, and transcription of G1/S genes in response to DNA damage. Several studies hint that regulation of forks is perhaps the most critical function of the intra-S checkpoint. However, the exact role of the checkpoint at replication forks has remained elusive and controversial. Is the checkpoint required for fork stability, or fork restart, or to prevent fork reversal or fork collapse, or activate repair at replication forks? What are the factors that the checkpoint targets at stalled replication forks? In this review, we will discuss the various pathways activated by the intra-S checkpoint in response to damage to prevent genomic instability.

【 授权许可】

Unknown