The functional roles of PML nuclear bodies in genome maintenance.

Abstract

In the nucleus, there are several membraneless structures called nuclear bodies. Among them, promyelocytic leukemia nuclear bodies (PML-NBs) are involved in multiple genome maintenance pathways including the DNA damage response, DNA repair, telomere homeostasis, and p53-associated apoptosis. In response to DNA damage, PML-NBs are coalesced and divided by a fission mechanism, thus increasing their number. PML-NBs also play a role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Clinically, the dominant negative PML-RARα fusion protein expressed in acute promyelocytic leukemia (APL) inhibits the transactivation of downstream factors and disrupts PML function, revealing the tumor suppressor role of PML-NBs. All-trans retinoic acid and arsenic trioxide treatment has been implemented for promyelocytic leukemia to target the PML-RARα fusion protein. PML-NBs are associated with various factors implicated in genome maintenance, and are found at the sites of DNA damage. Their interaction with proteins such as p53 indicates that PML-NBs may play a significant role in apoptosis and cancer. Decades of research have revealed the importance of PML-NBs in diverse cellular pathways, yet the underlying molecular mechanisms and exact functions of PML-NBs remain elusive. In this review, PML protein modifications and the functional relevance of PML-NB and its associated factors in genome maintenance will be discussed.

• Authors: Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan Kim
• Journal: Mutation research (Mutat Res) Vol. 809 Pg. 99-107 (05 2018) ISSN: 1873-135X [Electronic] Netherlands
• PMID: 28521962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Oncogene Proteins, Fusion
• Promyelocytic Leukemia Protein
• promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein
• PML protein, human

Topics

• Animals
• Apoptosis
• DNA Breaks, Double-Stranded
• DNA Repair
• Genomic Instability
• Humans
• Intranuclear Space (metabolism, pathology)
• Leukemia, Promyelocytic, Acute (genetics, metabolism, pathology)
• Oncogene Proteins, Fusion (genetics, metabolism)
• Promyelocytic Leukemia Protein (genetics, metabolism)
• Telomere Homeostasis