The histone acetyl transferase LdHAT1 from Leishmania donovani is regulated by S-phase cell cycle kinase.
Histone acetyl transferases (HATs) are important histone modifiers that affect critical cellular processes like transcription, DNA replication and repairs through highly dynamic chromatin remodelling. Our earlier studies recognized LdHAT1 as a substrate of the S-phase cell cycle kinase LdCyc1-CRK3 from Leishmania donovani. Here, we confirm through site-directed mutagenesis that RXL-like cyclin-binding (Cy) motif dependent interaction of LdHAT1 with LdCyc1 is essential for its phosphorylation at a canonical Cdk target site by the kinase complex. LdHAT1 acetylates K10 residue of a peptide derived from L. donovani histone H4 N-terminal tail. Interestingly, phosphorylation of LdHAT1 by the S-phase kinase inhibits its H4K10 acetylation activity, implicating an important mechanism of periodic regulation of histone acetylation during cell cycle progression.
Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India.
Anup Kumar
AK
Maity
Partha
P
Saha
D000107:Acetylation; D020816:Amino Acid Motifs; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D007893:Leishmania donovani / Q000737:chemistry / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D006657:Histones; D015800:Protozoan Proteins; D051548:Histone Acetyltransferases; D018844:Cyclin-Dependent Kinases