PUBLICATION

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Authors

Babu, S., Takeuchi, Y., Masai, I.

ID

ZDB-PUB-220810-2

Date

2022

Source

eLIFE 11: (Journal)

Registered Authors

Babu, Swathy, Masai, Ichiro, Takeuchi, Yuki

Keywords

Banp, DNA damage, cell biology, cenpt, chromosome segregation, developmental biology, ncapg, tp53, zebrafish

MeSH Terms

Retina
Chromosomes
DNA Damage
Mitosis/genetics
Nuclear Proteins*/genetics
Cell Cycle/physiology
Zebrafish*/genetics
Animals
Chromosome Segregation

(all 9)

PubMed

35942692 Full text @ Elife

Abstract

Btg3-associated nuclear protein (Banp) was originally identified as a nuclear matrix-associated region (MAR)-binding protein and it functions as a tumor suppressor. At the molecular level, Banp regulates transcription of metabolic genes via a CGCG-containing motif called the Banp motif. However, its physiological roles in embryonic development are unknown. Here, we report that Banp is indispensable for the DNA damage response and chromosome segregation during mitosis. Zebrafish banp mutants show mitotic cell accumulation and apoptosis in developing retina. We found that DNA replication stress and tp53-dependent DNA damage responses were activated to induce apoptosis in banp mutants, suggesting that Banp is required for regulation of DNA replication and DNA damage repair. Furthermore, consistent with mitotic cell accumulation, chromosome segregation was not smoothly processed from prometaphase to anaphase in banp morphants, leading to a prolonged M-phase. Our RNA- and ATAC-sequencing identified 31 candidates for direct Banp target genes that carry the Banp motif. Interestingly, a DNA replication fork regulator, wrnip1, and two chromosome segregation regulators, cenpt and ncapg, are included in this list. Thus, Banp directly regulates transcription of wrnip1 for recovery from DNA replication stress, and cenpt and ncapg for chromosome segregation during mitosis. Our findings provide the first in vivo evidence that Banp is required for cell-cycle progression and cell survival by regulating DNA damage responses and chromosome segregation during mitosis.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
atm	banp^rw337/rw337	standard conditions	Long-pec	head	RTPCR	Fig. 3
atr	banp^rw337/rw337	standard conditions	Long-pec	head	RTPCR	Fig. 3
bbc3	banp^rw337/rw337	standard conditions	Long-pec	head	RTPCR	Fig. 3
ccng1	banp^rw337/rw337	standard conditions	Long-pec	head	RTPCR	Fig. 3
cdkn1a	banp^rw337/rw337	standard conditions	Long-pec	head	RTPCR	Fig. 3
cenpt	banp^rw337/rw337	standard conditions	Long-pec	head	RNA-Seq	Fig. 6
cenpt	banp^rw337/rw337	standard conditions	Long-pec	head	RTPCR	Fig. 5
cenpt	WT + MO1-banp	standard conditions	Long-pec	head	RTPCR	Fig. 5
GFP	banp^rw337/rw337; rw021Tg	standard conditions	Day 4	amacrine cell	IFL	Fig. 1
GFP	banp^rw337/rw337; rw021Tg	standard conditions	Day 4	photoreceptor cell	IFL	Fig. 1

1 - 10 of 21

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-banp	standard conditions	Prim-5	retina apoptotic chromosome condensation increased frequency, abnormal	Fig. 1
WT + MO1-banp	standard conditions	Prim-5	retina apoptotic process increased frequency, abnormal	Fig. 1
WT + MO1-banp	standard conditions	Prim-5	retinal outer plexiform layer decreased amount, abnormal	Fig. 1
WT + MO1-banp	standard conditions	Long-pec	head cenpt expression decreased amount, abnormal	Fig. 5
WT + MO1-banp	standard conditions	Long-pec	head ncapg expression decreased amount, abnormal	Fig. 5
WT + MO1-banp	standard conditions	Long-pec	head ab7-h2afx labeling increased amount, abnormal	Fig. 4
banp^rw337/rw337	standard conditions	Prim-5	retinal cell programmed cell death normal occurrence, normal	Fig. 2
banp^rw337/rw337	standard conditions	Prim-25	presumptive neural retina regulation of cell division normal process quality, normal	Fig. 1
banp^rw337/rw337	standard conditions	Long-pec	head atm expression increased amount, abnormal	Fig. 3
banp^rw337/rw337	standard conditions	Long-pec	head atr expression increased amount, abnormal	Fig. 3

1 - 10 of 70

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
kca6Tg	Tg(h2az2a:h2az2a-GFP)	Transgenic Insertion
kca66Tg	Tg(h2az2a:h2az2a-GFP)	Transgenic Insertion
oki011Tg	Tg(Xla.Eef1a1:gmnn-mCherry)	Transgenic Insertion
oki049Tg	Tg(Xla.Eef1a1:mCherry-CAAX)	Transgenic Insertion
rw021Tg	Tg(atoh7:GFP)	Transgenic Insertion
rw337		Point Mutation	banp
sa12976		Point Mutation	banp

1 - 7 of 7

Show

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
banp	MO1-banp	MRPHLNO
tp53	MO4-tp53	MRPHLNO
tp53	MO6-tp53	MRPHLNO

Fish

Fish
banp^rw337/rw337
banp^rw337/rw337 + MO4-tp53
banp^rw337/rw337 + MO6-tp53
banp^rw337/rw337; rw021Tg
kca6Tg; oki011Tg
kca6Tg; oki011Tg + MO1-banp
kca6Tg; oki011Tg + MO6-tp53
kca66Tg; oki011Tg
rw021Tg
WT

1 - 10 of 12

Show

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP
mCherry	EFG	mCherry

Mapping

Babu et al., 2022 ZDB-PUB-220810-2 PMID:35942692

Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina

Babu et al., 2022

ZDB-PUB-220810-2
PMID:35942692