The functional roles of PML nuclear bodies in genome maintenance.
Mutat Res
; 809: 99-107, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-28521962
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Promielocítica Aguda
/
Proteínas de Fusão Oncogênica
/
Espaço Intranuclear
/
Instabilidade Genômica
/
Reparo do DNA
/
Proteína da Leucemia Promielocítica
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mutat Res
Ano de publicação:
2018
Tipo de documento:
Article
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS