PMID- 16628214
OWN - NLM
STAT- MEDLINE
DCOM- 20060721
LR  - 20220129
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 25
IP  - 10
DP  - 2006 May 17
TI  - A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage 
      sites.
PG  - 2178-88
AB  - The BRCA1 tumour suppressor and its heterodimeric partner BARD1 constitute an 
      E3-ubiquitin (Ub) ligase and function in DNA repair by unknown mechanisms. We 
      show here that the Caenorhabditis elegans BRCA1/BARD1 (CeBCD) complex possesses 
      an E3-Ub ligase responsible for ubiquitylation at DNA damage sites following 
      ionizing radiation (IR). The DNA damage checkpoint promotes the association of 
      the CeBCD complex with E2-Ub conjugating enzyme, Ubc5(LET-70), leading to the 
      formation of an active E3-Ub ligase on chromatin following IR. Correspondingly, 
      defects in Ubc5(let-70) or the DNA damage checkpoint genes atl-1 or mre-11 
      abolish CeBCD-dependent ubiquitylation in vivo. Extending these findings to human 
      cells reveals a requirement for UbcH5c, the MRN complex, gamma-H2AX and a 
      co-dependence for ATM and ATR kinases for BRCA1-dependent ubiquitylation at DNA 
      damage sites. Furthermore, we demonstrate that the DNA damage checkpoint promotes 
      the association between BRCA1 and UbcH5c to form an active E3-Ub ligase on 
      chromatin after IR. These data reveal that BRCA1-dependent ubiquitylation is 
      activated at sites of DNA repair by the checkpoint as part of a conserved DNA 
      damage response.
FAU - Polanowska, Jolanta
AU  - Polanowska J
AD  - DNA Damage Response Laboratory, Cancer Research UK, London Research Institute, 
      Clare Hall Laboratories, South Mimms, UK.
FAU - Martin, Julie S
AU  - Martin JS
FAU - Garcia-Muse, Tatiana
AU  - Garcia-Muse T
FAU - Petalcorin, Mark I R
AU  - Petalcorin MI
FAU - Boulton, Simon J
AU  - Boulton SJ
LA  - eng
GR  - 2003:569/BCN_/Breast Cancer Now/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060420
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (BRCA1 Protein)
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Chromatin)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Ubiquitin)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.7.- (Rad51 Recombinase)
SB  - IM
MH  - Animals
MH  - BRCA1 Protein/genetics/*metabolism
MH  - Caenorhabditis elegans/genetics/metabolism
MH  - Caenorhabditis elegans Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Chromatin/metabolism
MH  - *DNA Damage
MH  - DNA Repair
MH  - Enzyme Activation
MH  - Humans
MH  - Multiprotein Complexes
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rad51 Recombinase/genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - Ubiquitin/*metabolism
MH  - Ubiquitin-Protein Ligases/genetics/metabolism
PMC - PMC1462971
EDAT- 2006/04/22 09:00
MHDA- 2006/07/22 09:00
PMCR- 2007/05/17
CRDT- 2006/04/22 09:00
PHST- 2005/11/02 00:00 [received]
PHST- 2006/03/28 00:00 [accepted]
PHST- 2006/04/22 09:00 [pubmed]
PHST- 2006/07/22 09:00 [medline]
PHST- 2006/04/22 09:00 [entrez]
PHST- 2007/05/17 00:00 [pmc-release]
AID - 7601102 [pii]
AID - 10.1038/sj.emboj.7601102 [doi]
PST - ppublish
SO  - EMBO J. 2006 May 17;25(10):2178-88. doi: 10.1038/sj.emboj.7601102. Epub 2006 Apr 
      20.