title: Maternal BCAS2 protects genomic integrity in mouse early embryonic development.
abstract: Mammalian early embryos maintain accurate genome integrity for proper development within a programmed timeline despite constant assaults on their DNA by replication, DNA demethylation and genetic defects transmitted from germ cells. However, how genome integrity is safeguarded during mammalian early embryonic development remains unclear. BCAS2 (breast carcinoma amplified sequence 2), a core component of the PRP19 complex involved in pre-mRNA splicing, plays an important role in the DNA damage response through the RPA complex, a key regulator in the maintenance of genome integrity. Currently, the physiological role of BCAS2 in mammals is unknown. We now report that BCAS2 responds to endogenous and exogenous DNA damage in mouse zygotes. Maternal depletion of BCAS2 compromises the DNA damage response in early embryos, leading to developmental arrest at the two- to four-cell stage accompanied by the accumulation of damaged DNA and micronuclei. Furthermore, BCAS2 mutants that are unable to bind RPA1 fail in DNA repair during the zygotic stage. In addition, phosphorylated RPA2 cannot localise to the DNA damage sites in mouse zygotes with disrupted maternal BCAS2. These data suggest that BCAS2 might function through the RPA complex during DNA repair in zygotes. Together, our results reveal that maternal BCAS2 maintains the genome integrity of early embryos and is essential for female mouse fertility.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qianhua
authors.initials: Q
authors.lastname: Xu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Fengchao
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhen-Ao
authors.initials: ZA
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xukun
authors.initials: X
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xing-Jiang
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhenjiang 310058, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: College of Biological Science and Engineering, Beijing University of Agriculture, Beijing 102206, China.
authors.forename: Zhaohong
authors.initials: Z
authors.lastname: Yi
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, China gaoshaorong@tongji.edu.cn lil@ioz.ac.cn.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China gaoshaorong@tongji.edu.cn lil@ioz.ac.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D011247:Pregnancy; D000072260:RNA Splicing Factors; D060888:Real-Time Polymerase Chain Reaction; D051716:Replication Protein A / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000605455:BCAS2 protein, mouse; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D034521:Nuclear Matrix-Associated Proteins; C518638:Prpf19 protein, mouse; D000072260:RNA Splicing Factors; D051716:Replication Protein A; C497168:Rpa1 protein, mouse
keywords: BCAS2; DNA damage; Genomic integrity; Maternal effect genes; Mouse early embryonic development