遗传 ›› 2019, Vol. 41 ›› Issue (12): 1084-1098.doi: 10.16288/j.yczz.19-158

• 综述 • 上一篇    下一篇

退火解旋酶SMARCAL1在维持基因组稳定中的作用与机制

文雅蕾1, 吕柯孬2, 徐小康1, 张欣1, 丁良1(), 潘学峰1,2,3()   

  1. 1. 河北大学医学院药理室,保定 071000
    2. 北京理工大学生命学院,北京 100081
    3. 河北大学化学与环境学院,保定 071000
  • 收稿日期:2019-07-07 修回日期:2019-09-04 出版日期:2019-12-20 发布日期:2019-09-18
  • 通讯作者: 丁良,潘学峰 E-mail:345823685@qq.com;xuefengpancam@aliyun.com
  • 作者简介:文雅蕾,硕士研究生,专业方向:分子药理学。E-mail: 491574395@qq.com
  • 基金资助:
    北京自然科学基金项目编号(5132014);河北省医学科学重点项目资助编号(20160051)

SMARCAL1, roles and mechanisms in genome stability maintenance

Wen Yalei1, Lü Kenao2, Xu Xiaokang1, Zhang Xin1, Ding Liang1(), Pan Xuefeng1,2,3()   

  1. 1. Department of Pharmacology, Medical College of Hebei University, Baoding 071000, China
    2. School of Life Science, Beijing Institute of Technology, Beijing 100081, China
    3. School of Chemistry and Environmental Science, Hebei University, Baoding 071000, China
  • Received:2019-07-07 Revised:2019-09-04 Online:2019-12-20 Published:2019-09-18
  • Contact: Ding Liang,Pan Xuefeng E-mail:345823685@qq.com;xuefengpancam@aliyun.com
  • Supported by:
    Supported by the Beijing Natural Science Foundation No(5132014);and the Hebei Provincial Key Research Programs for Medical Science No(20160051)

摘要:

SMARCAL1是属于SWI/SNF (SWItch/Sucrose Non-Fermentable)相关、基质相关和激动蛋白依赖的染色质调节因子家族成员ATP驱动的DNA退火解旋酶。SMARCAL1在体外和体内能催化单链结合蛋白RPA结合的DNA单链与其互补链退火成双链DNA。人Smarcal1基因的突变与Schimke免疫骨性发育不良(Schimke immuno-osseous dysplasia, SIOD)所能表现出的临床症状呈高度相关。本文对SMARCAL1在DNA损伤部位DNA复制叉的重塑、在DNA双链断裂(double-stranded DNA, dsDNA)处参与经典的非同源末端连接(non-homologous end joining, NHEJ)修复,以及在人染色体端粒完整性维护等方面的作用与机制进行了梳理,对Smarcal1基因突变类型与SIOD症状之间的对应关系进行了更新,并对SMARCAL1在三核苷酸重复序列扩增关联的神经-肌肉退行性病变过程中的可能作用进行了分析和讨论,旨在更好地理解该退火解旋酶在维持基因组稳定中的作用和机制。

关键词: SMARCAL1, RPA, DNA复制叉, SIOD, 三核苷酸重复序列扩增

Abstract:

SMARCAL1 is an ATP-driven DNA annealing helicase that is similar in structure to the chromatin regulators in the subfamily A group of the SWI/SNF-related matrix-associated actin-dependent chromatin regulators. SMARCAL1 catalyzes the formation of dsDNA by annealing the single-stranded binding protein RPA coated ssDNA with its complementary strand both in vitro and in vivo. In humans, different mutations of Smarcal1 gene are found to be closely related to different symptoms shown in individuals with Schimke immuno-osseous dysplasia (SIOD). This paper reviews the recent research progress of SMARCAL1 functions in remodeling DNA replication forks at damaged DNA sites, working in classical non-homologous end joining (NHEJ) repair of DNA double-stranded breaks, and in maintaining chromosomal telomere integrity. The relationships between the mutations of Smarcal1 gene in different SIOD symptoms, and the possible involvements of SMARCAL1 in neuromuscular degenerative diseases associated with trinucleotide repeats expansions are also updated and discussed to better understand the roles and mechanisms of the annealing helicase in genome stability maintenance.

Key words: SMARCAL1, RPA, DNA replication fork, SIOD, expansions of trinucleotide repeats