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The Molecular Mechanisms of DNA Replication and Repair

A Special Issue of Cancers (ISSN 2072-6694) belonging to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 1228

Editor


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Guest Editor
1. Department of Medicine, Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
2. Harvard Medical School, Boston, MA 02115, USA
Interests: DNA repair; DNA replication; NDRG1; MRE11; MRN complex; drug resistance

Special Issue Information

Dear Colleagues,

DNA replication is a fundamental process that duplicates genetic material prior to cell division. It begins with the unwinding of the double helix, followed by the synthesis of complementary strands by DNA polymerase in accordance with the A-T and C-G base-pairing rules. This semi-conservative mechanism produces two identical DNA molecules, each containing one original and one newly synthesized strand, thereby ensuring genetic stability and faithful inheritance. However, DNA can be damaged by environmental factors or replication errors. To address this, cells employ various DNA repair mechanisms, such as base excision repair, nucleotide excision repair, and mismatch repair, to correct these mistakes. These processes recognize and remove damaged bases or mismatched pairs, thereby restoring the correct DNA sequence. In cancer, tumor cells obtain DNA damage due to replication stress and as a consequence of DNA damaging chemotherapies. Tumor cells rely on effective DNA repair mechanisms to avoid cell death and to sustain cell proliferation. Collectively, replication and repair mechanisms maintain genome integrity, prevent mutations, and support normal cellular function and survival, as well as contribute to tumor fitness and chemoresistance. This Special Issue, entitled "The Molecular Mechanisms of DNA Replication and Repair", invites submissions of research articles and review manuscripts on related topics.

Dr. Taru Muranen
Guest Editor

Manuscript Submission Information

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Keywords

  • DNA replication
  • DNA repair
  • double helix
  • drug resistance

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Published Papers (1 paper)

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Research

22 pages, 2860 KB  
Article
Interaction of NDRG1 and MRE11 Modulates DNA Replication and Repair
by Hanna M. Doh, Nina Kozlova, Zhipeng A. Wang, Hwan Bae, Philip A. Cole and Taru Muranen
Cancers 2026, 18(8), 1303; https://doi.org/10.3390/cancers18081303 - 20 Apr 2026
Viewed by 931
Abstract
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Patients are treated with DNA damaging chemotherapies which act by inducing DNA damage in rapidly dividing tumor cells. Unfortunately, these tumors frequently develop treatment resistance, underscoring the need to [...] Read more.
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Patients are treated with DNA damaging chemotherapies which act by inducing DNA damage in rapidly dividing tumor cells. Unfortunately, these tumors frequently develop treatment resistance, underscoring the need to understand resistance mechanisms in order to develop better treatment strategies. DNA damage response (DDR) detects and repairs DNA damage, and the DDR pathway has been shown to contribute to chemoresistance. Another factor known to drive chemoresistance in PDAC is the dense stroma, composed of extracellular matrix proteins secreted by cancer-associated fibroblasts (CAFs). Our recent work identified a CAF-induced resistance mechanism involving N-myc downstream regulated gene 1 (NDRG1). CAF-induced signaling resulted in the phosphorylation of NDRG1 and NDRG1-dependent DNA repair and protection from chemotherapies. Loss of NDRG1 resulted in increased chemotherapy-induced DNA damage and decreased replication fork speed and recovery. Methods: To gain insight into the molecular mechanism of NDRG1-mediated DNA repair and replication, we performed a BioID screen to identify binding partners of NDRG1. We further assessed the mechanistic roles of the identified interaction partners on DNA repair using DNA replication and repair assays such as the Comet assay and DNA fiber assays. Results: Our BioID screen identified meiotic recombination 11 (MRE11) protein, a nuclease involved in DDR, as a putative NDRG1 interacting protein. Interaction between MRE11 and NDRG1 was enriched during the late S/early G2 cell cycle phases and under replication stress. However, this interaction is likely indirect as the interaction only occurred in a cellular context and not with in vitro purified proteins. Blocking NDRG1 phosphorylation or blocking MRE11 exonuclease activity both resulted in protection of newly synthesized DNA at stalled replication forks. In NDRG1 knockout cells, blocking MRE11 led to decreased protection of nascent DNA, suggesting that NDRG1 and MRE11 may be acting in the same pathway and that NDRG1 is required for MRE11’s activity at stalled forks. Conclusions: In summary, our work has uncovered a protein complex between NDRG1 and MRE11 that may play a key role in chemoresistance due to its role in the processing of stalled replication forks. Full article
(This article belongs to the Special Issue The Molecular Mechanisms of DNA Replication and Repair)
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