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Cell Mol Life Sci. 2019 Oct;76(19):3827-3841. doi: 10.1007/s00018-019-03208-z. Epub 2019 Jul 13.

The Tousled-like kinases regulate genome and epigenome stability: implications in development and disease.

Author information

1
Department of Oncology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, C/Baldiri Reixac 10, 08028, Barcelona, Spain. sandra.segura-bayona@crick.ac.uk.
2
The Francis Crick Institute, London, UK. sandra.segura-bayona@crick.ac.uk.
3
Department of Oncology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, C/Baldiri Reixac 10, 08028, Barcelona, Spain. travis.stracker@irbbarcelona.org.

Abstract

The Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine-threonine kinases that have been implicated in DNA replication, DNA repair, transcription, chromatin structure, viral latency, cell cycle checkpoint control and chromosomal stability in various organisms. The functions of the TLKs appear to depend largely on their ability to regulate the H3/H4 histone chaperone ASF1, although numerous TLK substrates have been proposed. Over the last few years, a clearer picture of TLK function has emerged through the identification of new partners, the definition of specific roles in development and the elucidation of their structural and biochemical properties. In addition, the TLKs have been clearly linked to human disease; both TLK1 and TLK2 are frequently amplified in human cancers and TLK2 mutations have been identified in patients with neurodevelopmental disorders characterized by intellectual disability (ID), autism spectrum disorder (ASD) and microcephaly. A better understanding of the substrates, regulation and diverse roles of the TLKs is needed to understand their functions in neurodevelopment and determine if they are viable targets for cancer therapy. In this review, we will summarize current knowledge of TLK biology and its potential implications in development and disease.

KEYWORDS:

ASF1A; ASF1B; Cancer; Cell cycle checkpoint; DNA repair; DNA replication; Epigenetics; Genome instability; Histone chaperone; Kinase; Neurodevelopmental disorder; TLK1; TLK2

PMID:
31302748
DOI:
10.1007/s00018-019-03208-z
[Indexed for MEDLINE]

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