Cyclin-dependent kinase-dependent phosphorylation of Lif1 and Sae2 controls imprecise nonhomologous end joining accompanied by double-strand break resection

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
Kenichiro MatsuzakiMiki Shinohara

Abstract

DNA double-strand breaks (DSBs) are repaired by two distinct pathways, homologous recombination (HR) and nonhomologous end joining (NHEJ). NHEJ includes two pathways, that is, precise and imprecise end joining. We found that Lif1, a component of the DNA ligase IV complex in Saccharomyces cerevisiae, was phosphorylated by cyclin-dependent kinase (CDK) at Ser261 during the S to G2 phase but not during G1 phase. This phosphorylation was required for efficient NHEJ in G2/M cells, rather than in G1 cells. It also promotes the stable binding of Lif1 protein to DSBs, specifically in G2/M-arrested cells, which shows the resection of DSB ends. Thus, Lif1 phosphorylation plays a critical role in a certain type of imprecise NHEJ accompanied by DSB end resection and micro-homology. Lif1 phosphorylation at Ser261 is probably involved in micro-homology-dependent end joining associated with producing single-stranded DSB ends that are formed by Sae2 as early intermediates in the HR pathway. CDK-dependent modification of the NHEJ pathway might make DSB ends compatible for NHEJ and thus prevent competition between HR and NHEJ in hierarchy on the choice of DSB repair pathways.

References

Feb 24, 1989·Cell·B J Thomas, R Rothstein
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·U H MortensenR Rothstein
Jul 31, 1997·Nature·T E WilsonM R Lieber
Feb 5, 1998·Nature·A Shinohara, T Ogawa
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·T SugiyamaS C Kowalczykowski
Jun 10, 1998·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·A ShinoharaT Ogawa
Dec 5, 1998·Microbiology and Molecular Biology Reviews : MMBR·M D Mendenhall, A E Hodge
Oct 13, 1999·Molecular Cell·D DurocherS P Jackson
Feb 19, 2000·Current Biology : CB·S H Teo, S P Jackson
Nov 29, 2002·Microbiology and Molecular Biology Reviews : MMBR·Lorraine S Symington
Jul 29, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kentaro YamashitaAkira Shinohara
Nov 16, 2005·Annual Review of Genetics·James M DaleyThomas E Wilson
Nov 30, 2005·Molecular and Cellular Biology·Phillip L PalmbosThomas E Wilson
Jun 26, 2007·Nature Structural & Molecular Biology·Yu ZhangAlan E Tomkinson
Oct 17, 2007·Nature Reviews. Microbiology·Stewart Shuman, Michael S Glickman
Nov 15, 2007·The Journal of Biological Chemistry·Michael R Lieber
Feb 5, 2008·Genetics·Hee-Sook KimJohn H J Petrini
Feb 5, 2008·Genes & Development·Lihong WanNancy M Hollingsworth
Aug 22, 2008·Nature·Pablo HuertasStephen P Jackson
Sep 23, 2008·Nature·Eleni P Mimitou, Lorraine S Symington
Oct 17, 2008·Genes & Development·Serge GravelStephen P Jackson
Sep 10, 2010·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Zhihui ZhuAkira Shinohara
Oct 18, 2011·Nature·Valerie GarciaMatthew J Neale

❮ Previous
Next ❯

Citations

Apr 11, 2013·Nucleic Acids Research·Dana VigasovaLumir Krejci
Mar 13, 2014·Nature Structural & Molecular Biology·Sarah K DengLorraine S Symington
Nov 8, 2015·Biochemical and Biophysical Research Communications·Naoko Tanaka, Yukio Mukai
Oct 7, 2015·Trends in Biochemical Sciences·Agnel Sfeir, Lorraine S Symington
Feb 4, 2014·FEMS Microbiology Reviews·David P Mathiasen, Michael Lisby
Dec 24, 2014·Cell Reports·Pierre HentgesAidan J Doherty
Apr 23, 2013·Journal of Molecular Biology·Camilla TrovesiMaria Pia Longhese
May 10, 2015·DNA Repair·James M DaleyPatrick Sung
Nov 13, 2012·Trends in Biochemical Sciences·Wytse BruinsmaRené H Medema
Dec 1, 2015·Genes & Genetic Systems·Yuichiro SaitoJunya Kobayashi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.