A human BRCA2 complex containing a structural DNA binding component influences cell cycle progression.
Germline mutations of the human BRCA2 gene confer susceptibility to breast cancer. Although the function of the BRCA2 protein remains to be determined, murine cells homozygous for BRCA2 inactivation display chromosomal aberrations. We have isolated a 2 MDa BRCA2-containing complex and identified a structural DNA binding component, designated as BRCA2-Associated Factor 35 (BRAF35). BRAF35 contains a nonspecific DNA binding HMG domain and a kinesin-like coiled coil domain. Similar to BRCA2, BRAF35 mRNA expression levels in mouse embryos are highest in proliferating tissues with high mitotic index. Strikingly, nuclear staining revealed a close association of BRAF35/BRCA2 complex with condensed chromatin coincident with histone H3 phosphorylation. Importantly, antibody microinjection experiments suggest a role for BRCA2/BRAF35 complex in modulation of cell cycle progression.
Marmorstein
L Y
LY
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Kinev
A V
AV
Chan
G K
GK
Bochar
D A
DA
Beniya
H
H
Epstein
J A
JA
Yen
T J
TJ
Shiekhattar
R
R
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000737:chemistry; D002843:Chromatin / Q000378:metabolism*; D002875:Chromosomes / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006609:High Mobility Group Proteins; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008845:Microinjections; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D010051:Ovarian Neoplasms / Q000235:genetics; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000906:Antibodies; D024682:BRCA2 Protein; D002843:Chromatin; D004268:DNA-Binding Proteins; C000625244:HMG20B protein, human; D006609:High Mobility Group Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors