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The functional roles of PML nuclear bodies in genome maintenance

Authors
Chang, Hae RyungMunkhjargal, AnudariKim, Myung-JinPark, Seon YoungJung, EunyoungRyu, Jae-HaYang, YoungLim, Jong-SeokKim, Yonghwan
Issue Date
May-2018
Publisher
ELSEVIER SCIENCE BV
Keywords
PML nuclear body; SUMOylation; DNA repair; Genome maintenance
Citation
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, v.809, pp 99 - 107
Pages
9
Journal Title
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume
809
Start Page
99
End Page
107
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/4536
DOI
10.1016/j.mrfmmm.2017.05.002
ISSN
0027-5107
1873-135X
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-RARa 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-RARa 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.
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