PMID- 28058110
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2056-5968 (Print)
IS  - 2056-5968 (Electronic)
IS  - 2056-5968 (Linking)
VI  - 2
DP  - 2016
TI  - Bloom syndrome complex promotes FANCM recruitment to stalled replication forks 
      and facilitates both repair and traverse of DNA interstrand crosslinks.
PG  - 16047
LID - 10.1038/celldisc.2016.47 [doi]
AB  - The recruitment of FANCM, a conserved DNA translocase and key component of 
      several DNA repair protein complexes, to replication forks stalled by DNA 
      interstrand crosslinks (ICLs) is a step upstream of the Fanconi anemia (FA) 
      repair and replication traverse pathways of ICLs. However, detection of the FANCM 
      recruitment has been technically challenging so that its mechanism remains 
      exclusive. Here, we successfully observed recruitment of FANCM at stalled forks 
      using a newly developed protocol. We report that the FANCM recruitment depends 
      upon its intrinsic DNA translocase activity, and its DNA-binding partner FAAP24. 
      Moreover, it is dependent on the replication checkpoint kinase, ATR; but is 
      independent of the FA core and FANCD2-FANCI complexes, two essential components 
      of the FA pathway, indicating that the FANCM recruitment occurs downstream of ATR 
      but upstream of the FA pathway. Interestingly, the recruitment of FANCM requires 
      its direct interaction with Bloom syndrome complex composed of BLM helicase, 
      Topoisomerase 3alpha, RMI1 and RMI2; as well as the helicase activity of BLM. We 
      further show that the FANCM-BLM complex interaction is critical for replication 
      stress-induced FANCM hyperphosphorylation, for normal activation of the FA 
      pathway in response to ICLs, and for efficient traverse of ICLs by the 
      replication machinery. Epistasis studies demonstrate that FANCM and BLM work in 
      the same pathway to promote replication traverse of ICLs. We conclude that FANCM 
      and BLM complex work together at stalled forks to promote both FA repair and 
      replication traverse pathways of ICLs.
FAU - Ling, Chen
AU  - Ling C
AD  - Lab of Genetics, National Institute on Aging, National Institute of Health , 
      Baltimore, MD, USA.
FAU - Huang, Jing
AU  - Huang J
AD  - Lab of Molecular Gerontology, National Institute on Aging, National Institute of 
      Health , Baltimore, MD, USA.
FAU - Yan, Zhijiang
AU  - Yan Z
AD  - Lab of Genetics, National Institute on Aging, National Institute of Health , 
      Baltimore, MD, USA.
FAU - Li, Yongjiang
AU  - Li Y
AD  - Lab of Genetics, National Institute on Aging, National Institute of Health , 
      Baltimore, MD, USA.
FAU - Ohzeki, Mioko
AU  - Ohzeki M
AD  - Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation 
      Biology Center, Kyoto University , Kyoto, Japan.
FAU - Ishiai, Masamichi
AU  - Ishiai M
AD  - Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation 
      Biology Center, Kyoto University , Kyoto, Japan.
FAU - Xu, Dongyi
AU  - Xu D
AD  - Lab of Genetics, National Institute on Aging, National Institute of Health , 
      Baltimore, MD, USA.
FAU - Takata, Minoru
AU  - Takata M
AD  - Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation 
      Biology Center, Kyoto University , Kyoto, Japan.
FAU - Seidman, Michael
AU  - Seidman M
AD  - Lab of Molecular Gerontology, National Institute on Aging, National Institute of 
      Health , Baltimore, MD, USA.
FAU - Wang, Weidong
AU  - Wang W
AD  - Lab of Genetics, National Institute on Aging, National Institute of Health , 
      Baltimore, MD, USA.
LA  - eng
PT  - Journal Article
DEP - 20161220
PL  - England
TA  - Cell Discov
JT  - Cell discovery
JID - 101661034
PMC - PMC5167996
OTO - NOTNLM
OT  - BLM
OT  - Bloom syndrome
OT  - FANCM
OT  - Fanconi anemia
OT  - RMI2
OT  - interstrand crosslinks
OT  - replication
EDAT- 2017/01/07 06:00
MHDA- 2017/01/07 06:01
PMCR- 2016/12/20
CRDT- 2017/01/07 06:00
PHST- 2016/08/02 00:00 [received]
PHST- 2016/11/10 00:00 [accepted]
PHST- 2017/01/07 06:00 [entrez]
PHST- 2017/01/07 06:00 [pubmed]
PHST- 2017/01/07 06:01 [medline]
PHST- 2016/12/20 00:00 [pmc-release]
AID - celldisc201647 [pii]
AID - 10.1038/celldisc.2016.47 [doi]
PST - epublish
SO  - Cell Discov. 2016 Dec 20;2:16047. doi: 10.1038/celldisc.2016.47. eCollection 
      2016.