PXD018322

PXD018322 is an original dataset announced via ProteomeXchange.

Title	The Bloom Syndrome Complex Senses RPA-Coated Single-Stranded DNA to Restart Stalled Replication Forks
Description	The Bloom syndrome helicase BLM interacts with topoisomerase IIIa (TOP3A), RMI1 and RMI2 to form the BTR complex, which dissolves double Holliday junctions to produce non-crossover products during homologous recombination (HR). BLM also promotes DNA-end resection and stalled replication fork restart. However, it is still unclear how the activities of the BTR complex are regulated in cells. Here, we identify multiple highly conserved short linear peptide motifs within the BTR complex that interact cooperatively with RPA. Furthermore, we demonstrate that RPA-binding is essential for stable recruitment of BLM to DNA damage sites and for stalled fork restart, but not for its roles in HR. Disruption of RPA-binding thus constitutes a novel separation-of-function mutation of the BTR complex, and suggest a model in which BTR contains the intrinsic ability to measure levels of RPA-ssDNA at replication forks, which controls its recruitment and activation in response to replication stress.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:38:49.954.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018322
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	iolanda Vendrell
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-01 08:11:05	ID requested
⏵ 1	2024-10-07 10:38:50	announced

10.6019/PXD018322;

submitter keyword: Bloom syndrome,DNA damage response, BLM, RPA, homologous recombination, replication stress

Andrew N. Blackford
contact affiliation	1.MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK 2.CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK
contact email	andrew.blackford@imm.ox.ac.uk
lab head
iolanda Vendrell
contact affiliation	CRUK-MRC Oxford Institute for Radiation Oncology, Oxford University
contact email	iolanda.vendrell@oncology.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018322
     1. Label: PRIDE project
     2. Name: The Bloom Syndrome Complex Senses RPA-Coated Single-Stranded DNA to Restart Stalled Replication Forks