FlyBase Allele Report: Dmel\nbs[1]

General Information

Symbol

Dmel\nbs¹

Species

D. melanogaster

Name

FlyBase ID

FBal0009778

Feature type

allele

Associated gene

Dmel\nbs

Associated Insertion(s)

Carried in Construct

Key Links

Genomic Maps

JBrowse

Allele class

amorphic allele - genetic evidence

Mutagen

ethyl methanesulfonate

Nature of the Allele

Allele class

amorphic allele - genetic evidence

(Ciapponi et al., 2006, Bi et al., 2005)

Mutagen

ethyl methanesulfonate

Progenitor genotype

Cytology

Description

238bp deletion resulting in a frameshift that alters the amino acid sequence from positions 507-517 and introduces a stop codon at position 518.

(Ciapponi et al., 2006)

Contains a 238bp deletion and 1bp insertion that disrupts the open reading frame.

(Oikemus et al., 2006)

239bp deletion ( 3L:9695216..9695455 , release 4 genome annotation). The deletion results in a frameshift that terminates 11 codons after the deletion junction.

(Bi et al., 2005)

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

deletion

3L:9,721,270..9,721,507 [-]

Comment:

Reported as a 239 bp deletion which results in a frameshift that terminates 11 codons after the deletion junction. The genomic location was reported with respect to R4 coordinates. The annotated deletion is 238 bp and leads to the described frameshift.

(Bi et al., 2005)

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

Expression Data

Reporter Expression

Additional Information

Statement

Reference

Marker for

Reflects expression of

Reporter construct used in assay

Human Disease Associations

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 0 )

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{T12.Aβ42.UAS.Tag:SS(nec)}

(Tuxworth et al., 2019)

ameliorates Huntington's disease

modeled by Hsap\HTT^128Q.FL.UAS

(Tuxworth et al., 2019)

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal DNA repair (with nbs^SM9)

(Mukherjee et al., 2009)

abnormal DNA repair | dominant

(Mukherjee et al., 2009)

abnormal mitotic cell cycle (with Df(3R)PG4)

(Oikemus et al., 2006)

abnormal mitotic cell cycle | larval stage

(Cenci et al., 2015)

increased cell death

(Oikemus et al., 2006)

increased cell death (with nbs²)

(Oikemus et al., 2006)

lethal | larval stage | recessive

(Ciapponi et al., 2006)

lethal | pupal stage | recessive

(Ciapponi et al., 2006)

lethal - all die before end of P-stage

(Oikemus et al., 2006, Leicht and Bonner, 1988)

lethal - all die before end of P-stage (with nbs²)

(Oikemus et al., 2006)

lethal - all die before end of pupal stage | recessive

(Bi et al., 2005)

radiation sensitive

(Ciapponi et al., 2006)

radiation sensitive (with nbs^EY15506)

(Mukherjee et al., 2009)

radiation sensitive (with nbs^SM9)

(Mukherjee et al., 2009)

some die during pharate adult stage

(Oikemus et al., 2006, Leicht and Bonner, 1988)

some die during pharate adult stage (with nbs²)

(Oikemus et al., 2006)

some die during pupal stage | recessive

(Bi et al., 2005)

viable (with nbs^EY15506)

(Mukherjee et al., 2009)

Phenotype Manifest In

chromosome, telomeric region

(Ciapponi et al., 2006)

chromosome, telomeric region (with Df(3L)AC1)

(Ciapponi et al., 2006)

chromosome & neuroblast | third instar larval stage 2

(Bi et al., 2005)

chromosome | larval stage

(Cenci et al., 2015)

condensed chromosome

(Ciapponi et al., 2006)

condensed chromosome (with Df(3L)AC1)

(Ciapponi et al., 2006)

eye

(Ciapponi et al., 2006, Oikemus et al., 2006)

eye (with nbs²)

(Oikemus et al., 2006)

imaginal disc

(Ciapponi et al., 2006)

larval brain | third instar larval stage

(Merigliano et al., 2017)

larval neuroblast

(Cenci et al., 2015)

macrochaeta

(Oikemus et al., 2006)

macrochaeta (with nbs²)

(Oikemus et al., 2006)

nuclear chromosome | third instar larval stage

(Merigliano et al., 2017)

ommatidium

(Ciapponi et al., 2006)

Detailed Description

Statement

Reference

nbs¹/nbs¹ third instar larval brains exhibit higher frequency of cells with chromosome aberrations and telomeric fusions than controls.

(Merigliano et al., 2017)

In nbs¹ homozygous larvae, neuroblasts exhibit telomeric fusions, particularly in autosomes.

(Cenci et al., 2015)

nbs¹/nbs^SM9 and nbs¹/nbs^EY15506 larvae are hypersensitive to gamma irradiation compared to controls.

The total percentage of progeny representing repair in studies of excision and repair events of P{hsw^a} is similar in heterozygous flies and wild-type controls. However, the fraction of repair events that are attributed to completed synthesis-dependent strand annealing (SDSA) is significantly lower in heterozygotes than in wild type.

The total percentage of progeny representing repair in studies of excision and repair events of P{hsw^a} is similar in nbs¹/nbs^SM9 flies and wild-type controls. However, the fraction of repair events that are attributed to completed synthesis-dependent strand annealing (SDSA) is very low in nbs¹/nbs^SM9 flies compared to wild type. In the repair events that are not due to completed SDSA, the number of repair events that do not have evidence for synthesis is increased in the mutant flies compared to wild type, although synthesis is not entirely abolished. Synthesis tracts are significantly shorter in the mutant flies than in wild type.

The G2/M DNA damage-dependent cell cycle checkpoint induced by irradiation is nearly absent in homozygous mutant larvae at both low-dose (1000 rads) and high-dose (4000 rads). Heterozygotes also show loss of the checkpoint at low-dose irradiation and a significant weakening of the checkpoint at high-dose irradiation.

nbs¹/nbs^EY15506 larvae show loss of the G2/M DNA damage-dependent cell cycle checkpoint at low-dose irradiation (1000 rads) and a significant weakening of the checkpoint at high-dose irradiation (4000 rads).

(Mukherjee et al., 2009)

Most homozygotes and hemizygotes die at late larval or pupal stages, although a few animals survive to become pharate adults which have small and rough eyes.

The imaginal discs of mutants are often small and misshapen and very frequently have apoptotic cells.

Homozygous larval brains have high frequencies of both telomeric associations and chromosome breaks. Telomeric associations involve all chromosome ends. In homozygotes, the mean frequency of total telomeric associations seen in metaphases is 35.3%, with 7.15% being single telomeric associations (a single telomere is joined with either its sister telomere or another nonsister telomere) and 28.14% being double telomeric associations (a pair of sister telomeres are joined with another pair). 10.4% of metaphases have chromatid or isochromatid breaks. 3.6% of metaphase cells are polyploid or hyperploid.

In nbs¹/Df(3L)AC1 larval brains, the mean frequency of total telomeric associations seen in metaphases is 30.9%, with 9.7% being single telomeric associations (a single telomere is joined with either its sister telomere or another nonsister telomere) and 21.2% being double telomeric associations (a pair of sister telomeres are joined with another pair). 10.4% of metaphases have chromatid or isochromatid breaks. 0.3% of metaphase cells are polyploid or hyperploid.

Mutants treated with 1Gy of X rays show approximately 10-fold more chromosome breaks than wild-type controls.

(Ciapponi et al., 2006)

Flies homozygous for the nbs¹ mutation die as pharate adults with rough eyes and missing or abnormal bristles.

nbs¹/nbs² mutant flies die as pharate adults with rough eyes and missing or abnormal bristles.

The developing wings of nbs¹ mutant animals exhibit high levels of spontaneous apoptosis compared to wild-type animals. X-irradiation of these wing discs does not induce the rapid, large increase in apoptosis observed in wild-type wing discs.

nbs¹ mutant wing discs fail to arrest in response to a range of irradiation doses.

nbs¹ and nbs¹/Df(3R)PG4 mutant cells exhibit DNA breaks and telomere fusions in metaphase and anaphase.

nbs¹ mutants exhibit a severe effect on repair of DNA breaks, suggesting that nbs¹ mutant cells may also have reduced joining of unprotected telomeres.

(Oikemus et al., 2006)

Third instar larval neuroblasts from nbs¹ mutants have an average of 1.9 telomere fusions per nucleus.

(Bi et al., 2005)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

nbs¹ has abnormal mitotic cell cycle phenotype, enhanceable by cav^unspecified

(Oikemus et al., 2006)

nbs¹ has abnormal mitotic cell cycle phenotype, enhanceable by mus304^D2

(Oikemus et al., 2006)

NOT Enhanced by

Statement

Reference

nbs¹ has abnormal mitotic cell cycle phenotype, non-enhanceable by tefu¹

(Oikemus et al., 2006)

Suppressed by

Statement

Reference

nbs¹ has increased cell death phenotype, suppressible by tefu¹

(Oikemus et al., 2006)

nbs¹ has increased cell death phenotype, suppressible by lok^p6

(Oikemus et al., 2006)

nbs¹ has increased cell death phenotype, suppressible by p53^unspecified

(Oikemus et al., 2006)

Enhancer of

Statement

Reference

nbs¹ is an enhancer of abnormal mitotic cell cycle phenotype of cav^unspecified

(Oikemus et al., 2006)

nbs¹ is an enhancer of abnormal mitotic cell cycle phenotype of mus304^D2

(Oikemus et al., 2006)

NOT Enhancer of

Statement

Reference

nbs¹ is a non-enhancer of abnormal mitotic cell cycle phenotype of tefu¹

(Oikemus et al., 2006)

Suppressor of

Statement

Reference

nbs¹ is a suppressor of increased cell death phenotype of tefu¹

(Oikemus et al., 2006)

Other

Statement

Reference

nbs¹, tws⁴³⁰ has lethal - all die before end of larval stage phenotype

(Merigliano et al., 2017)

Phenotype Manifest In

Enhanced by

Statement

Reference

nbs¹ has chromosome, telomeric region phenotype, enhanceable by tefu^atm-6

(Ciapponi et al., 2006)

nbs¹ has condensed chromosome phenotype, enhanceable by tefu^atm-6

(Ciapponi et al., 2006)

nbs¹ has chromosome, telomeric region phenotype, enhanceable by mei-41^29D

(Ciapponi et al., 2006)

nbs¹ has condensed chromosome phenotype, enhanceable by mei-41^29D

(Ciapponi et al., 2006)

nbs¹ has chromosome, telomeric region phenotype, enhanceable by rad50^Δ5.1

(Ciapponi et al., 2006)

nbs¹ has chromosome & neuroblast | third instar larval stage 2 phenotype, enhanceable by mei-41^RT1

(Bi et al., 2005)

nbs¹ has chromosome & neuroblast | third instar larval stage 2 phenotype, enhanceable by mei-41^29D

(Bi et al., 2005)

NOT Enhanced by

Statement

Reference

nbs¹ has condensed chromosome phenotype, non-enhanceable by rad50^Δ5.1

(Ciapponi et al., 2006)

nbs¹ has chromosome & neuroblast | third instar larval stage 2 phenotype, non-enhanceable by mre11^unspecified

(Bi et al., 2005)

NOT suppressed by

Statement

Reference

nbs¹ has condensed chromosome phenotype, non-suppressible by rad50^Δ5.1

(Ciapponi et al., 2006)

nbs¹ has chromosome & neuroblast | third instar larval stage 2 phenotype, non-suppressible by mre11^unspecified

(Bi et al., 2005)

Enhancer of

Statement

Reference

nbs¹ is an enhancer of chromosome, telomeric region phenotype of rad50^Δ5.1

(Ciapponi et al., 2006)

nbs¹ is an enhancer of chromosome, telomeric region phenotype of tefu^atm-6

(Ciapponi et al., 2006)

nbs¹ is an enhancer of condensed chromosome phenotype of tefu^atm-6

(Ciapponi et al., 2006)

nbs¹ is an enhancer of chromosome, telomeric region phenotype of mei-41^29D

(Ciapponi et al., 2006)

nbs¹ is an enhancer of condensed chromosome phenotype of mei-41^29D

(Ciapponi et al., 2006)

NOT Enhancer of

Statement

Reference

nbs¹ is a non-enhancer of condensed chromosome phenotype of rad50^Δ5.1

(Ciapponi et al., 2006)

Suppressor of

Statement

Reference

nbs¹/nbs¹ is a suppressor | partially of nuclear chromosome | third instar larval stage phenotype of tws⁴³⁰

(Merigliano et al., 2017)

nbs¹/nbs¹ is a suppressor | partially of larval brain | third instar larval stage phenotype of tws⁴³⁰

(Merigliano et al., 2017)

NOT Suppressor of

Statement

Reference

nbs¹ is a non-suppressor of condensed chromosome phenotype of rad50^Δ5.1

(Ciapponi et al., 2006)

Additional Comments

Genetic Interactions

Statement

Reference

tws⁴³⁰/tws⁴³⁰ enhances the increased frequency of cells with chromosome aberrations while it partially suppresses the telomeric fusions of nbs¹/nbs¹ third instar larval brains.

(Merigliano et al., 2017)

The frequency of total telomeric associations and the frequency of chromosome breaks seen in metaphases of nbs¹ tefu^atm-6 larval brains is significantly increased compared that seen in each single mutant.

The frequency of total telomeric associations and the frequency of chromosome breaks seen in metaphases of mei-41^29D nbs¹ larval brains is significantly increased compared that seen in each single mutant.

The frequency of total telomeric associations seen in metaphases of rad50^Δ5.1 nbs¹ larval brains is significantly increased compared that seen in each single mutant, while the frequency of chromosome breaks in the double mutant is not significantly different from that seen in each single mutant.

(Ciapponi et al., 2006)

nbs¹ tefu¹ double mutants fail to exhibit high levels of apoptosis and fail to induce further apoptosis following irradiation, as in the nbs¹ single mutant.

Apoptosis is substantially reduced in nbs¹ lok^p6 double mutant third instar larval wing discs compared to nbs¹ single mutants.

Apoptosis is substantially reduced in nbs¹ p53^unspecified double mutant third instar larval wing discs compared to nbs¹ single mutants.

nbs¹ tefu¹ double mutant cells exhibit DNA breaks and telomere fusions in metaphase and anaphase.

nbs¹ tefu¹ double mutant cells exhibit similar fusion rates as tefu¹ single mutants, indicating that these genes act in a common telomere protection pathway.

nbs¹ mus304^D2 double mutant cells exhibit more DNA breaks and telomere fusions in metaphase and anaphase than in wild-type cells.

nbs¹ cav^unspecified mutant cells exhibit DNA breaks and telomere fusions in metaphase and anaphase, resulting in approximately 6.2 fusions/cell, compared to 0.02 in wild-type.

(Oikemus et al., 2006)

mre11^unspecified does not enhance or suppress the telomere fusion phenotype seen in third instar larval neuroblasts due to nbs¹. The presence of mei-41^29D or mei-41^RT1 leads to a synergistic increase in the rate of telomere fusion in these cells: nbs¹; mei-41^RT1 nuclei have 2.5 times as many as nbs¹ single mutants. Over 12% of the double mutant nuclei are polyploid (n = 106).

(Bi et al., 2005)

Xenogenetic Interactions

Statement

Reference

Complementation and Rescue Data

Rescued by

nbs¹ is rescued by nbs^+t5.2

(Bi et al., 2005)

Comments

nbs^+t5.2 completely rescues the lethality and telomere fusion defects of nbs¹ mutants.

(Bi et al., 2005)

Images (0)

Mutant

Wild-type

Stocks (2)

Bloomington

2554

nbs¹ kni^ri-1 p^p/TM3, Sb¹

Kyoto

107399

nbs¹ kni^ri-1 p^p/TM3, Sb¹

Notes on Origin

Discoverer

Leicht.

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (7)

Reported As

Symbol Synonym

l(3)67BDp

(Ciapponi et al., 2006)

l(3)67BDp¹

(Oikemus et al., 2006)

l(3)67BDp^e105A3

(Leicht and Bonner, 1988)

l(3)e105A3

lethal(3)67BDp¹

(Bi et al., 2005, Bi et al., 2005)

nbs1¹

(Colmenares et al., 2017)

nbs¹

(Porrazzo et al., 2022, Li et al., 2021, Tuxworth et al., 2019, Merigliano et al., 2017, Cenci et al., 2015, Morciano et al., 2013, Mukherjee et al., 2009, Ciapponi et al., 2006, Bi et al., 2005, Bi et al., 2005)

Name Synonyms

Secondary FlyBase IDs

References (14)

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