A dual role for UVRAG in maintaining chromosomal stability independent of autophagy.

Abstract:

:Autophagy defects have recently been associated with chromosomal instability, a hallmark of human cancer. However, the functional specificity and mechanism of action of autophagy-related factors in genome stability remain elusive. Here we report that UVRAG, an autophagic tumor suppressor, plays a dual role in chromosomal stability, surprisingly independent of autophagy. We establish that UVRAG promotes DNA double-strand-break repair by directly binding and activating DNA-PK in nonhomologous end joining. Disruption of UVRAG increases genetic instability and sensitivity of cells to irradiation. Furthermore, UVRAG was also found to be localized at centrosomes and physically associated with CEP63, an integral component of centrosomes. Disruption of the association of UVRAG with centrosomes causes centrosome instability and aneuploidy. UVRAG thus represents an autophagy-related molecular factor that also has a convergent role in patrolling both the structural integrity and proper segregation of chromosomes, which may confer autophagy-independent tumor suppressor activity.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Zhao Z,Oh S,Li D,Ni D,Pirooz SD,Lee JH,Yang S,Lee JY,Ghozalli I,Costanzo V,Stark JM,Liang C

doi

10.1016/j.devcel.2011.12.027

subject

Has Abstract

pub_date

2012-05-15 00:00:00

pages

1001-16

issue

5

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(12)00136-0

journal_volume

22

pub_type

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