Related Experiment Video
Updated: Jan 31, 2026
10:24
Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
14.6K
circPCMTD1: a protein-coding circular RNA that regulates DNA damage response in BCR/ABL1-positive leukemias
Dimitrios Papaioannou1, Amog P Urs2, Rémi Buisson3
1Division of Hematology & Medical Oncology, Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY.
Blood
|January 29, 2026
Summary
Circular RNA circPCMTD1 depletion inhibits leukemia cell proliferation by activating DNA damage response pathways. Targeting circPCMTD1 represents a potential therapeutic strategy for BCR/ABL1-positive myeloid leukemias.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are emerging regulators of cellular functions in both health and disease.
- BCR/ABL1-positive myeloid leukemias are characterized by specific genetic translocations driving leukemogenesis.
Purpose of the Study:
- To investigate the functional role of circPCMTD1 in BCR/ABL1-positive myeloid leukemias.
- To elucidate the molecular mechanisms underlying circPCMTD1's function and its potential as a therapeutic target.
Main Methods:
- circPCMTD1 depletion using screening experiments.
- RNA sequencing and mass cytometry for pathway analysis.
- DNA fiber assays, Comet assays, and Western blotting for genotoxic stress markers.
- In vivo studies in mouse models.
- Identification and characterization of circPCMTD1-derived peptide (cPCMTD1-127aa) and its interactions.
Main Results:
- circPCMTD1 depletion significantly inhibited leukemic cell proliferation and induced DNA damage response (DDR).
- Targeting circPCMTD1 activated DDR pathways and increased genotoxic stress in both cell lines and patient samples.
- In vivo, circPCMTD1 knockdown prolonged survival in mice with BCR/ABL1-positive leukemia.
- circPCMTD1 produces a peptide (cPCMTD1-127aa) that interacts with BCR/ABL1 and the BTR complex, enhancing DNA repair tolerance.
Conclusions:
- circPCMTD1 is functionally relevant in BCR/ABL1-positive myeloid leukemias.
- circPCMTD1 acts as a crucial regulator of leukemic cell survival and genome stability.
- circPCMTD1 and its peptide product cPCMTD1-127aa represent a potential therapeutic vulnerability in these leukemias.
Related Concept Videos
01:45Positive Regulator Molecules
136.2K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
136.2K
02:39Positive Regulator Molecules
6.9K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
6.9K
03:06From DNA to Protein
22.3K
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
22.3K
02:39lncRNA - Long Non-coding RNAs
9.9K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.9K
02:04Covalently Linked Protein Regulators
9.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.6K
02:36RNA Polymerase II Accessory Proteins
11.0K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
11.0K