The functional roles of PML nuclear bodies in genome maintenance

Publication date: May 2018Source: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Volume 809Author(s): Hae Ryung Chang, Anudari Munkhjargal, Myung-Jin Kim, Seon Young Park, Eunyoung Jung, Jae-Ha Ryu, Young Yang, Jong-Seok Lim, Yonghwan KimAbstractIn 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-RARĪ± 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-RARĪ± 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 unde...
Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - Category: Cytology Source Type: research