Nucleophagy contributes to genome stability through degradation of type II topoisomerases A and B and nucleolar components

Author:

Muciño-Hernández Gabriel1,Acevo-Rodríguez Pilar Sarah1,Cabrera-Benitez Sandra2ORCID,Guerrero Adán Oswaldo3ORCID,Merchant-Larios Horacio4ORCID,Castro-Obregón Susana1ORCID

Affiliation:

1. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México 1 Departamento de Neurodesarrollo y Fisiología, División de Neurociencias , , 04510 Mexico City , México

2. Facultad de Ciencias, Universidad Nacional Autónoma de México 2 , 04510 Mexico City , México

3. Laboratorio Nacional de Microscopía Avanzada, Instituto de Biotecnología, Universidad Nacional Autónoma de México 3 , 62210 Cuernavaca, Morelos , Mexico

4. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México 4 Departamento de Biología Celular y Fisiología , , 04510 Mexico City , Mexico

Abstract

ABSTRACT The nuclear architecture of mammalian cells can be altered as a consequence of anomalous accumulation of nuclear proteins or genomic alterations. Most of the knowledge about nuclear dynamics comes from studies on cancerous cells. How normal healthy cells maintain genome stability, avoiding accumulation of nuclear damaged material, is less understood. Here, we describe that primary mouse embryonic fibroblasts develop a basal level of nuclear buds and micronuclei, which increase after etoposide-induced DNA double-stranded breaks. Both basal and induced nuclear buds and micronuclei colocalize with the autophagic proteins BECN1 and LC3B (also known as MAP1LC3B) and with acidic vesicles, suggesting their clearance by nucleophagy. Some of the nuclear alterations also contain autophagic proteins and type II DNA topoisomerases (TOP2A and TOP2B), or the nucleolar protein fibrillarin, implying they are also targets of nucleophagy. We propose that basal nucleophagy contributes to genome and nuclear stability, as well as in response to DNA damage.

Funder

Consejo Nacional de Ciencia y Tecnología

Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México

Universidad Nacional Autónoma de México

Chan Zuckerberg Initiative

Publisher

The Company of Biologists

Subject

Cell Biology

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