GSBS Student Publications

Title

grp (chk1) replication-checkpoint mutations and DNA damage trigger a Chk2-dependent block at the Drosophila midblastula transition

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine; Department of Molecular Genetics and Microbiology

Date

4-6-2007

Document Type

Article

Medical Subject Headings

Animals; Blastula; DNA Damage; Drosophila; Drosophila Proteins; Embryonic Development; Female; Male; Protein Kinases; Protein-Serine-Threonine Kinases; Signal Transduction

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The 13 syncytial cleavage divisions that initiate Drosophila embryogenesis are under maternal genetic control. The switch to zygotic regulation of development at the midblastula transition (MBT) follows mitosis 13, when the cleavage divisions terminate, transcription increases and the blastoderm cellularizes. Embryos mutant for grp, which encodes Checkpoint kinase 1 (Chk1), are DNA-replication-checkpoint defective and fail to cellularize, gastrulate or to initiate high-level zygotic transcription at the MBT. The mnk (also known as loki) gene encodes Checkpoint kinase 2 (Chk2), which functions in DNA-damage signal transduction. We show that mnk grp double-mutant embryos are replication-checkpoint defective but cellularize, gastrulate and activate high levels of zygotic gene expression. We also show that grp mutant embryos accumulate DNA double-strand breaks and that DNA-damaging agents induce a mnk-dependent block to cellularization and zygotic gene expression. We conclude that the DNA-replication checkpoint maintains genome integrity during the cleavage divisions, and that checkpoint mutations lead to DNA damage that induces a novel Chk2-dependent block at the MBT.

Rights and Permissions

Citation: Development. 2007 May;134(9):1737-44. Epub 2007 Apr 4. Link to article on publisher's site

DOI of Published Version

10.1242/dev.02831

Related Resources

Link to Article in PubMed

Journal Title

Development (Cambridge, England)

PubMed ID

17409117