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Review
. 2019 Feb 14;20(4):816.
doi: 10.3390/ijms20040816.

MRN (MRE11-RAD50-NBS1) Complex in Human Cancer and Prognostic Implications in Colorectal Cancer

Yiling Situ  1 , Liping Chung  2   3 , Cheok Soon Lee  4   5   6   7   8   9 , Vincent Ho  10
Affiliations
Review

MRN (MRE11-RAD50-NBS1) Complex in Human Cancer and Prognostic Implications in Colorectal Cancer

Yiling Situ et al. Int J Mol Sci. .

Abstract

The MRE11-RAD50-NBS1 (MRN) complex has been studied in multiple cancers. The identification of MRN complex mutations in mismatch repair (MMR)-defective cancers has sparked interest in its role in colorectal cancer (CRC). To date, there is evidence indicating a relationship of MRN expression with reduced progression-free survival, although the significance of the MRN complex in the clinical setting remains controversial. In this review, we present an overview of the function of the MRN complex, its role in cancer progression, and current evidence in colorectal cancer. The evidence indicates that the MRN complex has potential utilisation as a biomarker and as a putative treatment target to improve outcomes of colorectal cancer.

Keywords: DNA damage response; MRE11-RAD50-NBS1 complex; biomarkers; colorectal cancer; prognosis; radiosensitivity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The MRN complex and the DNA-damage response. (A) Domain structure of MRE11, RAD50 and NBS1 proteins. (B) Model of intermolecular interaction of the MRN complex within the DNA damage response (DDR) pathway, illustrating the initial steps of DDR including exogenous insult (lightning symbol) and the recruitment of MRN complex to the site of DSB by interactions with γ-H2AX (black arrow). See text for details. CXXC, zinc hook; FHA, Forkhead associated domain; BRCT, BRAC1 carboxyl terminus domain; γ-H2AX, the phosphorylated form of H2AX; PARP1, Poly [ADP-ribose] polymerase 1; MDC1, mediator of DNA Damage Checkpoint 1.
See this image and copyright information in PMC

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