Related Experiment Video
Updated: May 24, 2025

Visualization of DNA Repair Proteins Interaction by Immunofluorescence
Published on: June 26, 2020
Chromatin assembly factor 1 subunit A promotes TLS pathway by recruiting E3 ubiquitin ligase RAD18 in cancer cells
Bing Wen1, Hai-Xiang Zheng2, Jing-Hua Heng2
1The Key Laboratory of Molecular Biology for the High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, 515041, Guangdong, P.R. China.
Abstract:
The translesion DNA synthesis (TLS) pathway mediated by proliferating cell nuclear antigen (PCNA) monoubiquitination is an essential mechanism by which cancer cells bypass DNA damage caused by DNA damage to maintain genomic stability and cell survival. Chromatin assembly factor 1 subunit A (CHAF1A) traditionally promotes histone assembly during DNA replication. Here, we revealed that CHAF1A is a novel regulator of the TLS pathway in cancer cells. CHAF1A promotes restart and elongation of the replication fork under DNA replication stress. Mechanistically, the C-terminal domain of CHAF1A directly interacts with E3 ubiquitin ligase RAD18, enhancing RAD18 binding on the stalled replication fork. CHAF1A facilitates PCNA K164 monoubiquitination mediated by RAD18, thereby promoting the recruitment of Y-family DNA polymerases and enhancing cancer cell resistance to DNA damage. In addition, CHAF1A-mediated RAD18 recruitment and PCNA monoubiquitination are independent of the CHAF1A-PCNA interaction and its histone assembly function. Taken together, these findings improve our understanding of the mechanisms that regulate the TLS pathway and provide insights into the relationship between CHAF1A and DNA replication stress in cancer cells.
More Related Videos
09:58Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
09:52A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
Published on: December 4, 2018
Related Concept Videos
DNA Damage can Stall the Cell Cycle
Restarting Stalled Replication Forks
Translesion DNA Polymerases
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Transcription Elongation Factors
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The Ras Gene
Ras is a...