Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund-Thomson syndrome.
Animals
Chromatin
/ metabolism
Chromosomal Instability
/ genetics
Chromosome Segregation
/ genetics
Codon, Nonsense
/ genetics
DNA Repair
DNA Replication
Frameshift Mutation
/ genetics
HEK293 Cells
HeLa Cells
Humans
Kinetochores
/ metabolism
Metaphase
/ genetics
Microtubule-Associated Proteins
/ genetics
Microtubules
/ metabolism
Ovum
/ enzymology
RecQ Helicases
/ genetics
Rothmund-Thomson Syndrome
/ enzymology
Spindle Apparatus
/ enzymology
Xenopus
/ genetics
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
01
07
2018
revised:
25
01
2019
accepted:
25
01
2019
entrez:
6
2
2019
pubmed:
6
2
2019
medline:
6
2
2019
Statut:
epublish
Résumé
RecQ-like helicase 4 (RECQL4) is mutated in patients suffering from the Rothmund-Thomson syndrome, a genetic disease characterized by premature aging, skeletal malformations, and high cancer susceptibility. Known roles of RECQL4 in DNA replication and repair provide a possible explanation of chromosome instability observed in patient cells. Here, we demonstrate that RECQL4 is a microtubule-associated protein (MAP) localizing to the mitotic spindle. RECQL4 depletion in M-phase-arrested frog egg extracts does not affect spindle assembly per se, but interferes with maintaining chromosome alignment at the metaphase plate. Low doses of nocodazole depolymerize RECQL4-depleted spindles more easily, suggesting abnormal microtubule-kinetochore interaction. Surprisingly, inter-kinetochore distance of sister chromatids is larger in depleted extracts and patient fibroblasts. Consistent with a role to maintain stable chromosome alignment, RECQL4 down-regulation in HeLa cells causes chromosome misalignment and delays mitotic progression. Importantly, these chromosome alignment defects are independent from RECQL4's reported roles in DNA replication and damage repair. Our data elucidate a novel function of RECQL4 in mitosis, and defects in mitotic chromosome alignment might be a contributing factor for the Rothmund-Thomson syndrome.
Identifiants
pubmed: 30718377
pii: 2/1/e201800120
doi: 10.26508/lsa.201800120
pmc: PMC6362308
pii:
doi:
Substances chimiques
Chromatin
0
Codon, Nonsense
0
Microtubule-Associated Proteins
0
RECQL4 protein, human
EC 3.6.1.-
RecQ Helicases
EC 3.6.4.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019 Yokoyama et al.
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