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Promyelocytic leukemia proteins regulate fanconi anemia gene expression

Authors
 Anudari Munkhjargal  ;  Myung-Jin Kim  ;  Da-Yeon Kim  ;  Young-Jun Jeon  ;  Young-Hoon Kee  ;  Lark-Kyun Kim  ;  Yong-Hwan Kim 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(15) : 7782, 2021-07 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Issue Date
2021-07
Keywords
PML nuclear body ; Fanconi anemia; interstrand DNA crosslink ; CHK1 inhibitors
Abstract
Abstract: Promyelocytic leukemia (PML) protein is the core component of subnuclear structures called PML nuclear bodies that are known to play important roles in cell survival, DNA damage responses, and DNA repair. Fanconi anemia (FA) proteins are required for repairing interstrand DNA crosslinks (ICLs). Here we report a novel role of PML proteins, regulating the ICL repair pathway. We found that depletion of the PML protein led to the significant reduction of damage-induced FANCD2 mono-ubiquitination and FANCD2 foci formation. Consistently, the cells treated with siRNA against PML showed enhanced sensitivity to a crosslinking agent, mitomycin C. Further studies showed that depletion of PML reduced the protein expression of FANCA, FANCG, and FANCD2 via reduced transcriptional activity. Interestingly, we observed that damage-induced CHK1 phosphorylation was severely impaired in cells with depleted PML, and we demonstrated that CHK1 regulates FANCA, FANCG, and FANCD2 transcription. Finally, we showed that inhibition of CHK1 phosphorylation further sensitized cancer cells to mitomycin C. Taken together, these findings suggest that the PML is critical for damage-induced CHK1 phosphorylation, which is important for FA gene expression and for repairing ICLs
Files in This Item:
T202103406.pdf Download
DOI
10.3390/ijms22157782
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Lark Kyun(김락균) ORCID logo https://orcid.org/0000-0001-5983-4470
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184680
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