Human artificial chromosome (HAC) for measuring chromosome instability (CIN) and identification of genes required for proper chromosome transmission.


Journal

Experimental cell research
ISSN: 1090-2422
Titre abrégé: Exp Cell Res
Pays: United States
ID NLM: 0373226

Informations de publication

Date de publication:
15 02 2020
Historique:
received: 30 10 2019
revised: 20 12 2019
accepted: 22 12 2019
pubmed: 27 12 2019
medline: 27 10 2020
entrez: 27 12 2019
Statut: ppublish

Résumé

Chromosomal instability (CIN) is one of the characteristics of cancer inherent for tumor initiation and progression, which is defined as a persistent, high rate of gain/loss of whole chromosomes. In the vast majority of human tumors the molecular basis of CIN remains unknown. The development of a conceptually simple colony color sectoring assay that measures yeast artificial chromosome (YAC) loss provided a powerful genetic tool to assess the rate of chromosome mis-segregation and also identified 937 yeast genes involved in this process. Similarly, a human artificial chromosome (HAC)-based assay has been recently developed and applied to quantify chromosome mis-segregation events in human cells. This assay allowed identification of novel human CIN genes in the library of protein kinases. Among them are PINK1, TRIO, IRAK1, PNCK, and TAOK1. The HAC-based assay may be applied to screen siRNA, shRNA and CRISPR-based libraries to identify the complete spectrum of CIN genes. This will reveal new insights into mechanisms of chromosome segregation and may expedite the development of novel therapeutic strategies to target the CIN phenotype in cancer cells.

Identifiants

pubmed: 31877307
pii: S0014-4827(19)30693-7
doi: 10.1016/j.yexcr.2019.111805
pmc: PMC7029811
mid: NIHMS1548033
pii:
doi:

Substances chimiques

RNA, Small Interfering 0
Protein Kinases EC 2.7.-

Types de publication

Journal Article Research Support, N.I.H., Intramural Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

111805

Subventions

Organisme : Intramural NIH HHS
ID : Z99 CA999999
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC010413
Pays : United States

Informations de copyright

Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest All three authors declare that they have no conflicts of interests, financial or otherwise.

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Auteurs

Natalay Kouprina (N)

Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA. Electronic address: kouprinn@mail.nih.gov.

Mikhail Liskovykh (M)

Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.

Nikolai Petrov (N)

Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.

Vladimir Larionov (V)

Developmental Therapeutics Branch, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.

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Classifications MeSH