ABRAXAS1

This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. Pseudogenes of this gene are found on chromosomes 3 and 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

Full Name

Abraxas 1, BRCA1 A Complex Subunit

Function

Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of BRCA1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX.

Biological Process

Attachment of spindle microtubules to kinetochore
Chromatin organization
Double-strand break repair
Double-strand break repair via nonhomologous end joining
Mitotic spindle assembly
Positive regulation of DNA repair
Protein deubiquitination
Protein K63-linked deubiquitination
Response to ionizing radiation
Signal transduction involved in G2 DNA damage checkpoint

Cellular Location

Nucleus. Localizes at sites of DNA damage at double-strand breaks (DSBs).

Involvement in disease

A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.

PTM

Phosphorylation of Ser-406 of the pSXXF motif by ATM or ATR constitutes a specific recognition motif for the BRCT domain of BRCA1. Ionizing radiation promotes rapid phosphorylation at Ser-404 and Ser-406 by ATM; this promotes recruitment of BRCA1 to sites of DNA damage