Ultraviolet Radiation Stress Triggers the Down-regulation of Essential Replication Factor Mcm10

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Jan 13

PMID 20064936

Citations 16

Authors

Aparna Sharma

Manpreet Kaur

Ananya Kar

Sourabh M Ranade

Sandeep Saxena

Affiliations

Soon will be listed here.

Abstract

We report that upon UV radiation insult, mammalian cells specifically down-regulate Mcm10, a protein essential for the initiation and elongation phases of DNA replication. The levels of a majority of replication factors remain unaffected under this condition, implying that Mcm10 is a key node in the regulation of the replication machinery. High doses of ionizing gamma radiation and exposure to a combination of DNA-damaging chemicals do not decrease Mcm10 protein levels, demonstrating that Mcm10 down-regulation is triggered only by UV-specific damage. The decrease of Mcm10 protein levels is not caused by transcriptional inhibition or cleavage by apoptotic enzymes, but results from degradation by the 26 S proteasome. UV-triggered degradation of Mcm10 requires its linker or C-terminal domain. In addition, Mcm10 down-regulation is not limited to cells from a particular lineage. Therefore, our study reveals a mechanism by which mammalian cells effectively inhibit the replication machinery during stress to prevent it from drifting toward a catastrophic path of genomic instability.

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