Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

Fukumoto, Yasunori; Kuki, Kazumasa; Morii, Mariko; Miura, Takahito; Honda, Takeshi; Ishibashi, Keiichiro; Hasegawa, Hitomi; Kubota, Sho; Ide, Yudai; Yamaguchi, Noritaka; Nakayama, Yuji; Yamaguchi, Naoto

doi:10.1016/j.bbrc.2014.08.113

Cited by 9 publications

(5 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Active, sumoylated TRIM28 was shown to bind rapidly to damaged chromatin in association with HP1, followed by phosphorylation on S824 and reversal of the silencing effects of the factor. In addition, resolution of the DSB response appeared to involve the phosphorylation of TRIM28 in residues adjacent to the HP1 box by Src family kinases as discussed earlier [ 35 , 37 ]. Thus phosphorylation may counteract the repressive influence of TRIM28 by both reversing sumoylation of the BR domain and reducing association with HP1.…”

Section: Key Role For Trim28 In Dna Repairmentioning

confidence: 90%

“…There thus appeared to be cycle of SUMO- and phospho-S824 modifications that governed cycles of contrasting TRIM28 activity [ 35 ]. A further wrinkle to this regulatory pathway was provided by findings that members of the Src family of non-receptor tyrosine kinases could suppress ATM-mediated TRIM28 modification and, during DNA repair, signal the termination of DNA damage mediated checkpoint signaling [ 37 ].…”

Section: Trim28 a Multi-domain Proteinmentioning

confidence: 99%

See 1 more Smart Citation

TRIM28 as a novel transcriptional elongation factor

Bunch

Calderwood

2015

BMC Molecular Biol

View full text Add to dashboard Cite

TRIM28 is a multidomain protein with versatile functions in transcription and DNA repair. Recently it was shown that this factor plays unanticipated roles in transcriptional elongation. TRIM28 was shown to stabilize the pausing of RNA polymerase II (Pol II) close to the transcriptional start site in many unactivated genes, permitting Pol II accumulation and readying genes for induction. In addition, the factor was shown to respond rapidly to signals accompanying transcriptional activation permitting the productive elongation of RNA by previously paused Pol II. We discuss here critical regulatory mechanisms of TRIM28 in transcriptional control and DNA repair that may illuminate the novel roles of this factor in pausing and elongation of Pol II.

show abstract

Section: Key Role For Trim28 In Dna Repairmentioning

confidence: 90%

Section: Trim28 a Multi-domain Proteinmentioning

confidence: 99%

TRIM28 as a novel transcriptional elongation factor

Bunch

Calderwood

2015

BMC Molecular Biol

View full text Add to dashboard Cite

show abstract

“…Tyrosine kinases are also activated in cells following exposure to radiation, interact with DNA repair and checkpoint pathways, to promote survival or apoptosis ( 29 , 30 ). In addition, tyrosine kinases may directly terminate activated checkpoints ( 31 , 32 ). Further, both receptor and non-receptor tyrosine kinases epigenetically regulate DNA damage signaling by modifying the core histones as well as chromatin modifiers (Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

Cross talk of tyrosine kinases with the DNA damage signaling pathways

Mahajan¹,

Mahajan²

2015

Nucleic Acids Res

View full text Add to dashboard Cite

Tyrosine kinases respond to extracellular and intracellular cues by activating specific cellular signaling cascades to regulate cell cycle, growth, proliferation, differentiation and survival. Likewise, DNA damage response proteins (DDR) activated by DNA lesions or chromatin alterations recruit the DNA repair and cell cycle checkpoint machinery to restore genome integrity and cellular homeostasis. Several new examples have been uncovered in recent studies which reveal novel epigenetic and non-epigenetic mechanisms by which tyrosine kinases interact with DDR proteins to dictate cell fate, i.e. survival or apoptosis, following DNA damage. These studies reveal the ability of tyrosine kinases to directly regulate the activity of DNA repair and cell cycle check point proteins by tyrosine phosphorylation. In addition, tyrosine kinases epigenetically regulate DNA damage signaling pathways by modifying the core histones as well as chromatin modifiers at critical tyrosine residues. Thus, deregulated tyrosine kinase driven epigenomic alterations have profound implications in cancer, aging and genetic disorders. Consequently, targeting oncogenic tyrosine kinase induced epigenetic alterations has gained significant traction in overcoming cancer cell resistance to various therapies. This review discusses mechanisms by which tyrosine kinases interact with DDR pathways to regulate processes critical for maintaining genome integrity as well as clinical strategies for targeted cancer therapies.

show abstract

“…On the other hand, as SFK inhibition delayed S phase progression in the presence of a Chk1 inhibitor ( Figure 4A), mechanisms other than ATR-Chk1 signaling should be involved in the regulation of replication resumption by SFKs after replication fork collapse. One of the possible mechanisms is ATM signaling, because this is upregulated by SFK inhibition (Fukumoto et al, 2014c). These data also raise the possibility that SFK inhibition delayed resumption of replication through different mechanisms in the recovery from the normal replication checkpoint and from replication fork collapse.…”

Section: Discussionmentioning

confidence: 90%

Src family kinases maintain the balance between replication stress and the replication checkpoint

Miura

Fukumoto

Morii

et al. 2015

Cell Biology International

Self Cite

View full text Add to dashboard Cite

Progression of DNA replication is tightly controlled by replication checkpoints to ensure the accurate and rapid duplication of genetic information. Upon replication stress, the replication checkpoint slows global DNA replication by inhibiting the late-firing origins and by slowing replication fork progression. Activation of the replication checkpoint has been studied in depth; however, little is known about the termination of the replication checkpoint. Here, we show that Src family kinases promote the recovery from replication checkpoints. shRNA knockdown of a Src family kinase, Lyn, and acute chemical inhibition of Src kinases prevented inactivation of Chk1 after removal of replication stress. Consistently, Src inhibition slowed resumption of DNA replication, after the removal of replication blocks. The effect of Src inhibition was not observed in the presence of an ATM/ATR inhibitor caffeine. These data indicate that Src kinases promote the resumption of DNA replication by suppressing ATR-dependent replication checkpoints. Surprisingly, the resumption of replication was delayed by caffeine. In addition, Src inhibition delayed recovery from replication fork collapse. We propose that Src kinases maintain the balance between replication stress and the activity of the replication checkpoint.

show abstract

Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

Cited by 9 publications

References 42 publications

TRIM28 as a novel transcriptional elongation factor

TRIM28 as a novel transcriptional elongation factor

Cross talk of tyrosine kinases with the DNA damage signaling pathways

Src family kinases maintain the balance between replication stress and the replication checkpoint

Contact Info

Product

Resources

About