SMARCAD1 Phosphorylation and Ubiquitination Are Required for Resection during DNA Double-Strand Break Repair

被引：40

作者：

Chakraborty, Sharmistha ^{[1
]}

Pandita, Raj K. ^{[1
]}

Hambarde, Shashank ^{[1
]}

Mattoo, Abid R. ^{[1
]}

Charaka, Vijaya ^{[1
]}

Ahmed, Kazi M. ^{[1
]}

Iyer, Swaminathan P. ^{[2
]}

Hunt, Clayton R. ^{[1
]}

Pandita, Tej K. ^{[1
]}

机构：

[1] Weill Cornell Med Coll, Houston Methodist Res Inst, Houston Methodist Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[2] Weill Cornell Med Coll, Houston Methodist Res Inst, Houston Methodist Canc Ctr, Dept Hematol, Houston, TX 77030 USA

来源：

ISCIENCE | 2018年 / 2卷

关键词：

ATM PROTEIN-KINASE; GENOMIC INSTABILITY; DAMAGE RESPONSE; PATHWAY CHOICE; HUMAN-DISEASES; END RESECTION; IN-VIVO; CHROMATIN; REPLICATION; COMPLEX;

D O I：

10.1016/j.isci.2018.03.016

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The chromatin remodeling factor SMARCAD1, an SWI/SNF ATPase family member, has a role in 5' end resection at DNA double-strand breaks (DSBs) to produce single-strand DNA (ssDNA), a critical step for subsequent checkpoint and repair factor loading to remove DNA damage. However, the mechanistic details of SMARCAD1 coupling to the DNA damage response and repair pathways remains unknown. Here we report that SMARCAD1 is recruited to DNA DSBs through an ATM-dependent process. Depletion of SMARCAD1 reduces ionizing radiation (IR)-induced repairosome foci formation and DSB repair by homologous recombination (HR). IR induces SMARCAD1 phosphorylation at a conserved T906 by ATM kinase, a modification essential for SMARCAD1 recruitment to DSBs. Interestingly, T906 phosphorylation is also important for SMARCAD1 ubiquitination by RING1 at K905. Both these post-translational modifications are critical for regulating the role of SMARCAD1 in DNA end resection, HR-mediated repair, and cell survival after DNA damage.

引用

页码：123 / +

页数：28

共 53 条

[1] SMARCAD1, a novel human helicase family-defining member associated with genetic instability: Cloning, expression, and mapping to 4q22-q23, a band rich in breakpoints and deletion mutants involved in several human diseases [J].